Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 3, pp 340–351 | Cite as

Common Variable Immunodeficiency and Liver Involvement

  • Junmin Song
  • Ana Lleo
  • Guo Xiang Yang
  • Weici Zhang
  • Christopher L. Bowlus
  • M. Eric Gershwin
  • Patrick S. C. Leung
Article

Abstract

Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder, characterized by remarkable hypogammaglobulinemia. The disease can develop at any age without gender predominance. The prevalence of CVID varies widely worldwide. The underlying causes of CVID remain largely unknown; primary B-cell dysfunctions, defects in T cells and antigen-presenting cells are involved. Although some monogenetic defects have been identified in some CVID patients, it is likely that CVID is polygenic. Patients with CVID develop recurrent and chronic infections (e.g., bacterial infections of the respiratory or gastrointestinal tract), autoimmune diseases, lymphoproliferation, malignancies, and granulomatous lesions. Interestingly, autoimmunity can be the only clinical manifestation of CVID at the time of diagnosis and may even develop prior to hypogammaglobulinemia. The diagnosis of CVID is largely based on the criteria established by European Society for Immunodeficiencies and Pan-American Group for Immunodeficiency (ESID/PAGID) and with some recent modifications. The disease can affect multiple organs, including the liver. Clinical features of CVID patients with liver involvement include abnormal liver biochemistries, primarily elevation of alkaline phosphatase (ALP), nodular regenerative hyperplasia (NRH), or liver cirrhosis and its complications. Replacement therapy with immunoglobulin (Ig) and anti-infection therapy are the primary treatment regimen for CVID patients. No specific therapy for liver involvement of CVID is currently available, and liver transplantation is an option only in select cases. The prognosis of CVID varies widely. Further understanding in the etiology and pathophysiology will facilitate early diagnosis and treatments to improve prognosis.

Keywords

Common variable immunodeficiency CVID Primary immunodeficiency B cell Hypogammaglobulinemia Infection Autoimmunity Granuloma Liver involvement Nodular regenerative hyperplasia Alkaline phosphatase 

Abbreviations

AIE

Autoimmune enteropathy

AIHA

Autoimmune hemolytic anemia

ALP

Alkaline phosphatase

CID

Combined immunodeficiency

CVID

Common variable immunodeficiency

GLILD

Granulomatous and lymphocytic interstitial lung disease

IBD

inflammatory bowel disease

ICON

International Consensus Document

Ig

Immunoglobulin

IL

Interleukin

ITP

Idiopathic thrombocytopenia

IVIG

Intravenous immunoglobulin

NRH

Nodular regenerative hyperplasia

PBC

Primary biliary cholangitis

PSC

Primary sclerosing cholangitis

r-GT

Gamma glutamyl transpeptidase

SCIG

Subcutaneous immunoglobulin

SIgAD

Selective Immunoglobulin A deficiency

TLR

Toll-like receptor

Treg cell

Regulatory T cell

XLA

X-linked agammaglobulinemia

Notes

Compliance with Ethical Standards

This article does not contain any studies with human participants or animals performed by any of the authors.

The authors declare that they have no potential conflict of interest.

References

  1. 1.
    Aune TM, Crooke PS 3rd, Patrick AE, Tossberg JT, Olsen NJ, Spurlock CF 3rd (2017) Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants. J Autoimmun 81:99–109PubMedPubMedCentralGoogle Scholar
  2. 2.
    Bao Y, Cao X (2016) Epigenetic control of B cell development and B-cell-related immune disorders. Clin Rev Allergy Immunol 50:301–311PubMedGoogle Scholar
  3. 3.
    Messina N, Fulford T, O'Reilly L, Loh WX, Motyer JM, Ellis D, McLean C et al (2016) The NF-kappaB transcription factor RelA is required for the tolerogenic function of Foxp3(+) regulatory T cells. J Autoimmun 70:52–62PubMedGoogle Scholar
  4. 4.
    Saldana JI, Solanki A, Lau CI, Sahni H, Ross S, Furmanski AL, Ono M et al (2016) Sonic hedgehog regulates thymic epithelial cell differentiation. J Autoimmun 68:86–97PubMedPubMedCentralGoogle Scholar
  5. 5.
    Shaabani N, Khairnar V, Duhan V, Zhou F, Tur RF, Haussinger D, Recher M et al (2016) Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation. J Autoimmun 67:82–89PubMedGoogle Scholar
  6. 6.
    Taraldsrud E, Fevang B, Aukrust P, Beiske KH, Floisand Y, Froland S, Rollag H et al (2014) Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9. Clin Exp Immunol 175:439–448PubMedPubMedCentralGoogle Scholar
  7. 7.
    Taraldsrud E, Fevang B, Jorgensen SF, Moltu K, Hilden V, Tasken K, Aukrust P et al (2017) Defective IL-4 signaling in T cells defines severe common variable immunodeficiency. J Autoimmun 81:110–119PubMedGoogle Scholar
  8. 8.
    Vignesh P, Rawat A, Singh S (2017) An update on the use of immunomodulators in primary Immunodeficiencies. Clin Rev Allergy Immunol 52:287–303PubMedGoogle Scholar
  9. 9.
    Wong GK, Heather JM, Barmettler S, Cobbold M (2017) Immune dysregulation in immunodeficiency disorders: the role of T-cell receptor sequencing. J Autoimmun 80:1–9PubMedGoogle Scholar
  10. 10.
    Salzer U, Warnatz K, Peter HH (2012) Common variable immunodeficiency: an update. Arthritis Res Ther 14:223PubMedPubMedCentralGoogle Scholar
  11. 11.
    Marschall K, Hoernes M, Bitzenhofer-Gruber M, Jandus P, Duppenthaler A, Wuillemin WA, Rischewski J et al (2015) The Swiss National Registry for primary immunodeficiencies: report on the first 6 years’ activity from 2008 to 2014. Clin Exp Immunol 182:45–50PubMedPubMedCentralGoogle Scholar
  12. 12.
    Gathmann B, Grimbacher B, Beaute J, Dudoit Y, Mahlaoui N, Fischer A, Knerr V et al (2009) The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008. Clin Exp Immunol 157(Suppl 1):3–11PubMedPubMedCentralGoogle Scholar
  13. 13.
    Boyle JM, Buckley RH (2007) Population prevalence of diagnosed primary immunodeficiency diseases in the United States. J Clin Immunol 27:497–502PubMedGoogle Scholar
  14. 14.
    Ward C, Lucas M, Piris J, Collier J, Chapel H (2008) Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia. Clin Exp Immunol 153:331–337PubMedPubMedCentralGoogle Scholar
  15. 15.
    Fukushima K, Ueno Y, Kanegane H, Yamagiwa Y, Inoue J, Kido O, Nagasaki F et al (2008) A case of severe recurrent hepatitis with common variable immunodeficiency. Hepatol Res 38:415–420PubMedGoogle Scholar
  16. 16.
    Daniels JA, Torbenson M, Vivekanandan P, Anders RA, Boitnott JK (2009) Hepatitis in common variable immunodeficiency. Hum Pathol 40:484–488PubMedGoogle Scholar
  17. 17.
    Macura-Biegun A, Kowalczyk D (2002) Common variable immunodeficiency concomitant with liver cirrhosis—case report. Przegl Lek 59:472–473PubMedGoogle Scholar
  18. 18.
    Cunningham-Rundles C, Bodian C (1999) Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 92:34–48PubMedPubMedCentralGoogle Scholar
  19. 19.
    Graziano V, Pecoraro A, Mormile I, Quaremba G, Genovese A, Buccelli C, Paternoster M et al (2017) Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels. Clin Immunol 180:1–4PubMedGoogle Scholar
  20. 20.
    Edgar JD, Buckland M, Guzman D, Conlon NP, Knerr V, Bangs C, Reiser V et al (2014) The United Kingdom primary immune deficiency (UKPID) registry: report of the first 4 years’ activity 2008-2012. Clin Exp Immunol 175:68–78PubMedGoogle Scholar
  21. 21.
    Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ et al (2016) International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 4:38–59PubMedGoogle Scholar
  22. 22.
    Ishimura M, Takada H, Doi T, Imai K, Sasahara Y, Kanegane H, Nishikomori R et al (2011) Nationwide survey of patients with primary immunodeficiency diseases in Japan. J Clin Immunol 31:968–976PubMedGoogle Scholar
  23. 23.
    group. CTFPs. The French national registry of primary immunodeficiency diseases (2010) Clin Immunol 135:264–272Google Scholar
  24. 24.
    Xiao X, Miao Q, Chang C, Gershwin ME, Ma X (2014) Common variable immunodeficiency and autoimmunity—an inconvenient truth. Autoimmun Rev 13:858–864PubMedGoogle Scholar
  25. 25.
    Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C (2012) Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 119:1650–1657PubMedPubMedCentralGoogle Scholar
  26. 26.
    Gathmann B, Mahlaoui N, Gerard L, Oksenhendler E, Warnatz K, Schulze I, Kindle G et al (2014) Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol 134:116–126PubMedGoogle Scholar
  27. 27.
    Cunningham-Rundles C, Maglione PJ (2012) Common variable immunodeficiency. J Allergy Clin Immunol 129:1425–1426.e1423PubMedGoogle Scholar
  28. 28.
    Tseng CW, Lai KL, Chen DY, Lin CH, Chen HH (2015) The incidence and prevalence of common variable immunodeficiency disease in Taiwan, A population-based study. PLoS One 10:e0140473PubMedPubMedCentralGoogle Scholar
  29. 29.
    Oksenhendler E, Gerard L, Fieschi C, Malphettes M, Mouillot G, Jaussaud R, Viallard JF et al (2008) Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis 46:1547–1554PubMedGoogle Scholar
  30. 30.
    Groth C, Drager R, Warnatz K, Wolff-Vorbeck G, Schmidt S, Eibel H, Schlesier M et al (2002) Impaired up-regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID). Clin Exp Immunol 129:133–139PubMedPubMedCentralGoogle Scholar
  31. 31.
    van de Ven AA, Compeer EB, van Montfrans JM, Boes M (2011) B-cell defects in common variable immunodeficiency: BCR signaling, protein clustering and hardwired gene mutations. Crit Rev Immunol 31:85–98PubMedGoogle Scholar
  32. 32.
    Foerster C, Voelxen N, Rakhmanov M, Keller B, Gutenberger S, Goldacker S, Thiel J et al (2010) B cell receptor-mediated calcium signaling is impaired in B lymphocytes of type Ia patients with common variable immunodeficiency. J Immunol 184:7305–7313PubMedGoogle Scholar
  33. 33.
    Ahn S, Cunningham-Rundles C (2009) Role of B cells in common variable immune deficiency. Expert Rev Clin Immunol 5:557–564PubMedPubMedCentralGoogle Scholar
  34. 34.
    Sharifi L, Mirshafiey A, Rezaei N, Azizi G, Magaji Hamid K, Amirzargar AA, Asgardoon MH et al (2016) The role of toll-like receptors in B-cell development and immunopathogenesis of common variable immunodeficiency. Expert Rev Clin Immunol 12:195–207PubMedGoogle Scholar
  35. 35.
    Yu JE, Knight AK, Radigan L, Marron TU, Zhang L, Sanchez-Ramon S, Cunningham-Rundles C (2009) Toll-like receptor 7 and 9 defects in common variable immunodeficiency. J Allergy Clin Immunol 124:349-356–e341-343Google Scholar
  36. 36.
    Yu JE, Zhang L, Radigan L, Sanchez-Ramon S, Cunningham-Rundles C (2012) TLR-mediated B cell defects and IFN-alpha in common variable immunodeficiency. J Clin Immunol 32:50–60PubMedGoogle Scholar
  37. 37.
    Ochtrop ML, Goldacker S, May AM, Rizzi M, Draeger R, Hauschke D, Stehfest C et al (2011) T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood 118:309–318PubMedGoogle Scholar
  38. 38.
    Vodjgani M, Aghamohammadi A, Samadi M, Moin M, Hadjati J, Mirahmadian M, Parvaneh N et al (2007) Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications. J Investig Allergol Clin Immunol 17:321–328PubMedGoogle Scholar
  39. 39.
    Sanchez-Ramon S, Radigan L, Yu JE, Bard S, Cunningham-Rundles C (2008) Memory B cells in common variable immunodeficiency: clinical associations and sex differences. Clin Immunol 128:314–321PubMedPubMedCentralGoogle Scholar
  40. 40.
    Ko J, Radigan L, Cunningham-Rundles C (2005) Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol 116:37–41PubMedGoogle Scholar
  41. 41.
    Haymore BR, Mikita CP, Tsokos GC (2008) Common variable immune deficiency (CVID) presenting as an autoimmune disease: role of memory B cells. Autoimmun Rev 7:309–312PubMedGoogle Scholar
  42. 42.
    Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M et al (2008) The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 111:77–85PubMedGoogle Scholar
  43. 43.
    Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, Debre P et al (2003) Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol 23:385–400PubMedGoogle Scholar
  44. 44.
    Warnatz K, Denz A, Drager R, Braun M, Groth C, Wolff-Vorbeck G, Eibel H et al (2002) Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 99:1544–1551PubMedGoogle Scholar
  45. 45.
    Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, Rezaei N et al (2017) Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol 13:101–115PubMedGoogle Scholar
  46. 46.
    Azizi G, Rezaei N, Kiaee F, Tavakolinia N, Yazdani R, Mirshafiey A, Aghamohammadi A (2016) T-cell abnormalities in common variable immunodeficiency. J Investig Allergol Clin Immunol 26:233–243PubMedGoogle Scholar
  47. 47.
    Berron-Ruiz L, Lopez-Herrera G, Vargas-Hernandez A, Santos-Argumedo L, Lopez-Macias C, Isibasi A, Segura-Mendez NH et al (2016) Impaired selective cytokine production by CD4(+) T cells in common variable immunodeficiency associated with the absence of memory B cells. Clin Immunol 166-167:19–26PubMedGoogle Scholar
  48. 48.
    Yu GP, Chiang D, Song SJ, Hoyte EG, Huang J, Vanishsarn C, Nadeau KC (2009) Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease. Clin Immunol 131:240–253PubMedPubMedCentralGoogle Scholar
  49. 49.
    Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, Fieschi C et al (2008) Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 112:277–286PubMedGoogle Scholar
  50. 50.
    Malphettes M, Gerard L, Carmagnat M, Mouillot G, Vince N, Boutboul D, Berezne A et al (2009) Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis 49:1329–1338PubMedGoogle Scholar
  51. 51.
    Yong PF, Workman S, Wahid F, Exley A, Webster AD, Ibrahim MA (2008) Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency. Clin Immunol 127:34–42PubMedGoogle Scholar
  52. 52.
    Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Galicier L, Lepelletier Y, Webster D, Levy Y et al (2004) Common variable immunodeficiency is associated with defective functions of dendritic cells. Blood 104:2441–2443PubMedGoogle Scholar
  53. 53.
    Ochs HD (2014) Common variable immunodeficiency (CVID): new genetic insight and unanswered questions. Clin Exp Immunol 178(Suppl 1):5–6PubMedPubMedCentralGoogle Scholar
  54. 54.
    Bogaert DJ, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F (2016) Genes associated with common variable immunodeficiency: one diagnosis to rule them all? J Med Genet 53:575–590PubMedGoogle Scholar
  55. 55.
    Kotlarz D, Zietara N, Milner JD, Klein C (2014) Human IL-21 and IL-21R deficiencies: two novel entities of primary immunodeficiency. Curr Opin Pediatr 26:704–712PubMedGoogle Scholar
  56. 56.
    Abolhassani H, Wang N, Aghamohammadi A, Rezaei N, Lee YN, Frugoni F, Notarangelo LD et al (2014) A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency. J Allergy Clin Immunol 134:1375–1380PubMedPubMedCentralGoogle Scholar
  57. 57.
    Sekinaka Y, Mitsuiki N, Imai K, Yabe M, Yabe H, Mitsui-Sekinaka K, Honma K, et al (2017) Common variable immunodeficiency caused by FANC mutations. J Clin Immunol 37:434–444PubMedGoogle Scholar
  58. 58.
    Cunningham-Rundles C (2010) How I treat common variable immune deficiency. Blood 116:7–15PubMedPubMedCentralGoogle Scholar
  59. 59.
    Li J, Wei Z, Li YR, Maggadottir SM, Chang X, Desai A, Hakonarson H (1860) Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches. Biochim Biophys Acta 2016:2656–2663Google Scholar
  60. 60.
    Fernandez Romero DS, Juri MC, Paolini MV, Malbran A (2013) Common variable immunodeficiency. Epidemiology and clinical manifestations in 69 patients. Medicina B Aires 73:315–323PubMedGoogle Scholar
  61. 61.
    Busse PJ, Farzan S, Cunningham-Rundles C (2007) Pulmonary complications of common variable immunodeficiency. Ann Allergy Asthma Immunol 98:1–8 quiz 8-11, 43 PubMedGoogle Scholar
  62. 62.
    Atarod L, Raissi A, Aghamohammadi A, Farhoudi A, Khodadad A, Moin M, Pourpak Z et al (2003) A review of gastrointestinal disorders in patients with primary antibody immunodeficiencies during a 10-year period (1990-2000), in children hospital medical center. Iran J Allergy Asthma Immunol 2:75–79PubMedGoogle Scholar
  63. 63.
    Kralickova P, Mala E, Vokurkova D, Krcmova I, Pliskova L, Stepanova V, Bartos V et al (2014) Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports. Int Arch Allergy Immunol 163:69–74PubMedGoogle Scholar
  64. 64.
    Woodward J, Gkrania-Klotsas E, Kumararatne D (2017) Chronic norovirus infection and common variable immunodeficiency. Clin Exp Immunol 188:363–370Google Scholar
  65. 65.
    Herrera-Sanchez DA, Castilla-Rodriguez JL, Castrejon-Vazquez MI, Vargas-Camano ME, Medina-Torres EA, Blancas-Galicia L, Espinosa-Padilla SE (2015) Infection due to Mycobacterium bovis in common variable immunodeficiency. Rev Alerg Mex 62:75–82PubMedGoogle Scholar
  66. 66.
    Milligan KL, Jain AK, Garrett JS, Knutsen AP (2012) Gastric ulcers due to varicella-zoster reactivation. Pediatrics 130:e1377–e1381PubMedGoogle Scholar
  67. 67.
    Cunningham-Rundles C (2008) Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol 28(Suppl 1):S42–S45PubMedPubMedCentralGoogle Scholar
  68. 68.
    Agarwal S, Cunningham-Rundles C (2009) Autoimmunity in common variable immunodeficiency. Curr Allergy Asthma Rep 9:347–352PubMedPubMedCentralGoogle Scholar
  69. 69.
    Martin-Blondel G, Camara B, Selves J, Robic MA, Thebault S, Bonnet D, Alric L (2010) Etiology and outcome of liver granulomatosis: a retrospective study of 21 cases. Rev Med Interne 31:97–106PubMedGoogle Scholar
  70. 70.
    Unger S, Seidl M, van Schouwenburg P, Rakhmanov M, Bulashevska A, Frede N, Grimbacher B et al (2017) TH1 phenotype of T follicular helper cells indicates an IFNgamma-associated immune dysregulation in CD21low CVID patients. J Allergy Clin ImmunolGoogle Scholar
  71. 71.
    Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, Puccetti A et al (2016) Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmun Rev 15:877–882PubMedGoogle Scholar
  72. 72.
    Keller B, Stumpf I, Strohmeier V, Usadel S, Verhoeyen E, Eibel H, Warnatz K (2017) High SYK expression drives constitutive activation of CD21low B cells. J Immunol 198:4285–4292PubMedGoogle Scholar
  73. 73.
    Wehr C, Eibel H, Masilamani M, Illges H, Schlesier M, Peter HH, Warnatz K (2004) A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol 113:161–171PubMedGoogle Scholar
  74. 74.
    Chua I, Quinti I, Grimbacher B (2008) Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol 15:368–374PubMedGoogle Scholar
  75. 75.
    Abolhassani H, Aghamohammadi A, Imanzadeh A, Mohammadinejad P, Sadeghi B, Rezaei N (2012) Malignancy phenotype in common variable immunodeficiency. J Investig Allergol Clin Immunol 22:133–134PubMedGoogle Scholar
  76. 76.
    Reichenberger F, Wyser C, Gonon M, Cathomas G, Tamm M (2001) Pulmonary mucosa-associated lymphoid tissue lymphoma in a patient with common variable immunodeficiency syndrome. Respiration 68:109–112PubMedGoogle Scholar
  77. 77.
    da Silva SP, Resnick E, Lucas M, Lortan J, Patel S, Cunningham-Rundles C, Gatter K et al (2011) Lymphoid proliferations of indeterminate malignant potential arising in adults with common variable immunodeficiency disorders: unusual case studies and immunohistological review in the light of possible causative events. J Clin Immunol 31:784–791PubMedPubMedCentralGoogle Scholar
  78. 78.
    Cunningham-Rundles C, Cooper DL, Duffy TP, Strauchen J (2002) Lymphomas of mucosal-associated lymphoid tissue in common variable immunodeficiency. Am J Hematol 69:171–178PubMedGoogle Scholar
  79. 79.
    Gangemi S, Allegra A, Musolino C (2015) Lymphoproliferative disease and cancer among patients with common variable immunodeficiency. Leuk Res 39:389–396PubMedGoogle Scholar
  80. 80.
    Quinti I, Agostini C, Tabolli S, Brunetti G, Cinetto F, Pecoraro A, Spadaro G (2012) Malignancies are the major cause of death in patients with adult onset common variable immunodeficiency. Blood 120:1953–1954PubMedGoogle Scholar
  81. 81.
    Dhalla F, da Silva SP, Lucas M, Travis S, Chapel H (2011) Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme. Clin Exp Immunol 165:1–7PubMedPubMedCentralGoogle Scholar
  82. 82.
    Gemeinhardt M, Turck J, Piper B, Helmberger T, Nerlich A, Schepp W (2012) Adenocarcinoma of the stomach and neuroendocrine carcinoma of the colon in a 45-year-old male patient suffering from common variable immunodeficiency (CVID) and ulcerative colitis. Z Gastroenterol 50:1292–1295PubMedGoogle Scholar
  83. 83.
    Ardeniz O, Cunningham-Rundles C (2009) Granulomatous disease in common variable immunodeficiency. Clin Immunol 133:198–207PubMedPubMedCentralGoogle Scholar
  84. 84.
    Morimoto Y, Routes JM (2005) Granulomatous disease in common variable immunodeficiency. Curr Allergy Asthma Rep 5:370–375PubMedGoogle Scholar
  85. 85.
    Verbsky JW, Routes JM (2014) Sarcoidosis and common variable immunodeficiency: similarities and differences. Semin Respir Crit Care Med 35:330–335PubMedGoogle Scholar
  86. 86.
    Agarwal S, Mayer L (2013) Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol 11:1050–1063PubMedPubMedCentralGoogle Scholar
  87. 87.
    Daniels JA, Lederman HM, Maitra A, Montgomery EA (2007) Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol 31:1800–1812PubMedGoogle Scholar
  88. 88.
    Goel A, Elias JE, Eapen CE, Ramakrishna B, Elias E (2014) Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH)-newer insights into pathogenesis and emerging newer treatment options. J Clin Exp Hepatol 4:247–256PubMedPubMedCentralGoogle Scholar
  89. 89.
    Gandhi K, Parikh P, Aronow WS, Desai H, Amin H, Sharma M, Rubinstein A (2010) A case of explosive progression of hepatocellular carcinoma in a patient with common variable immunodeficiency (CVID). J Gastrointest Cancer 41:281–284PubMedGoogle Scholar
  90. 90.
    Malamut G, Ziol M, Suarez F, Beaugrand M, Viallard JF, Lascaux AS, Verkarre V et al (2008) Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities. J Hepatol 48:74–82PubMedGoogle Scholar
  91. 91.
    Fuss IJ, Friend J, Yang Z, He JP, Hooda L, Boyer J, Xi L et al (2013) Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol 33:748–758PubMedPubMedCentralGoogle Scholar
  92. 92.
    Manas MD, Marchan E, Gijon J, Martin F (2006) Nodular regenerative hyperplasia of the liver in a patient with common variable immunodeficiency. An Med Interna 23:395–397PubMedGoogle Scholar
  93. 93.
    Conley ME, Park CL, Douglas SD (1986) Childhood common variable immunodeficiency with autoimmune disease. J Pediatr 108:915–922PubMedGoogle Scholar
  94. 94.
    Hausser C, Virelizier JL, Buriot D, Griscelli C (1983) Common variable hypogammaglobulinemia in children. Clinical and immunologic observations in 30 patients. Am J Dis Child 137:833–837PubMedGoogle Scholar
  95. 95.
    Martire B, Gentile A, Francavilla R, De Santis A, De Mattia D (2005) Successful treatment with cyclosporine A of HCV-driven chronic liver disease mimicking autoimmune hepatitis in a patient with common variable immunodeficiency. Immunopharmacol Immunotoxicol 27:535–543PubMedGoogle Scholar
  96. 96.
    Mahdavinia M, Mirsaeidi M, Bishehsari F, McGrath K (2015) Primary sclerosing cholangitis in common variable immune deficiency. Allergol Int 64:187–189PubMedPubMedCentralGoogle Scholar
  97. 97.
    Holmes SN, Condliffe A, Griffiths W, Baxendale H, Kumararatne DS (2015) Familial hepatopulmonary syndrome in common variable immunodeficiency. J Clin Immunol 35:302–304PubMedGoogle Scholar
  98. 98.
    Schouten JN, Verheij J, Seijo S (2015) Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis 10:67PubMedPubMedCentralGoogle Scholar
  99. 99.
    Webb GJ, Hirschfield GM (2016) Using GWAS to identify genetic predisposition in hepatic autoimmunity. J Autoimmun 66:25–39PubMedGoogle Scholar
  100. 100.
    Conley ME, Notarangelo LD, Etzioni A (1999) Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 93:190–197PubMedGoogle Scholar
  101. 101.
    Chapel H (2016) Common variable immunodeficiency disorders (CVID)—diagnoses of exclusion, especially combined immune defects. J Allergy Clin Immunol Pract 4:1158–1159PubMedGoogle Scholar
  102. 102.
    Bertinchamp R, Gerard L, Boutboul D, Malphettes M, Fieschi C, Oksenhendler E (2016) Exclusion of patients with a severe T-cell defect improves the definition of common variable immunodeficiency. J Allergy Clin Immunol Pract 4:1147–1157PubMedGoogle Scholar
  103. 103.
    Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L et al (2007) Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol 120:776–794PubMedPubMedCentralGoogle Scholar
  104. 104.
    Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C et al (2015) Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for primary immunodeficiency 2015. J Clin Immunol 35:696–726PubMedPubMedCentralGoogle Scholar
  105. 105.
    Chapel H, Cunningham-Rundles C (2009) Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol 145:709–727PubMedPubMedCentralGoogle Scholar
  106. 106.
    Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R (2013) New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol 174:203–211PubMedPubMedCentralGoogle Scholar
  107. 107.
    Ameratunga R, Gillis D, Steele R (2016) Diagnostic criteria for common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 4:1017–1018PubMedGoogle Scholar
  108. 108.
    Ameratunga R, Brewerton M, Slade C, Jordan A, Gillis D, Steele R, Koopmans W et al (2014) Comparison of diagnostic criteria for common variable immunodeficiency disorder. Front Immunol 5:415PubMedPubMedCentralGoogle Scholar
  109. 109.
    Al Kindi M, Mundy J, Sullivan T, Smith W, Kette F, Smith A, Heddle R et al (2012) Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency. Clin Exp Immunol 167:275–281PubMedPubMedCentralGoogle Scholar
  110. 110.
    Szablewski V, Rene C, Costes V (2015) Indolent cytotoxic T cell lymphoproliferation associated with nodular regenerative hyperplasia: a common liver lesion in the context of common variable immunodeficiency disorder. Virchows Arch 467:733–740Google Scholar
  111. 111.
    Ravindran J, Gillis D, Rowland R, Heddle R (1995) Common variable immunodeficiency associated with nodular regenerative hyperplasia of the liver. Aust NZ J Med 25:741Google Scholar
  112. 112.
    Kasztalska K, Ciebiada M, Cebula-Obrzut B, Gorski P (2011) Intravenous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency disease: an open-label prospective study. Clin Drug Investig 31:299–307PubMedGoogle Scholar
  113. 113.
    Albin S, Cunningham-Rundles C (2014) An update on the use of immunoglobulin for the treatment of immunodeficiency disorders. Immunotherapy 6:1113–1126PubMedPubMedCentralGoogle Scholar
  114. 114.
    Eijkhout HW, van Der Meer JW, Kallenberg CG, Weening RS, van Dissel JT, Sanders LA, Strengers PF et al (2001) The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med 135:165–174PubMedGoogle Scholar
  115. 115.
    Stonebraker JS, Farrugia A, Gathmann B, Orange JS (2014) Modeling primary immunodeficiency disease epidemiology and its treatment to estimate latent therapeutic demand for immunoglobulin. J Clin Immunol 34:233–244PubMedGoogle Scholar
  116. 116.
    Bjoro K, Haaland T, Skaug K, Froland SS (1999) The spectrum of hepatobiliary disease in primary hypogammaglobulinaemia. J Intern Med 245:517–524PubMedGoogle Scholar
  117. 117.
    Wong GK, Goldacker S, Winterhalter C, Grimbacher B, Chapel H, Lucas M, Alecsandru D et al (2013) Outcomes of splenectomy in patients with common variable immunodeficiency (CVID): a survey of 45 patients. Clin Exp Immunol 172:63–72PubMedPubMedCentralGoogle Scholar
  118. 118.
    Boursiquot JN, Gerard L, Malphettes M, Fieschi C, Galicier L, Boutboul D, Borie R et al (2013) Granulomatous disease in CVID: retrospective analysis of clinical characteristics and treatment efficacy in a cohort of 59 patients. J Clin Immunol 33:84–95PubMedGoogle Scholar
  119. 119.
    Thatayatikom A, Thatayatikom S, White AJ (2005) Infliximab treatment for severe granulomatous disease in common variable immunodeficiency: a case report and review of the literature. Ann Allergy Asthma Immunol 95:293–300PubMedGoogle Scholar
  120. 120.
    Malphettes M, Oksenhendler E, Galicier L, Fieschi C (2008) Granulomatous disease in common variable immunodeficiency. Rev Med Interne 29:28–32PubMedGoogle Scholar
  121. 121.
    Franxman TJ, Howe LE, Baker JR Jr (2014) Infliximab for treatment of granulomatous disease in patients with common variable immunodeficiency. J Clin Immunol 34:820–827PubMedGoogle Scholar
  122. 122.
    Chen Y, Cameron A (2013) Aspergillosis after liver transplantation in the context of common variable immunodeficiency: case report. Transpl Infect Dis 15:540–544PubMedGoogle Scholar
  123. 123.
    Montalti R, Mocchegiani F, Vincenzi P, Svegliati Baroni G, Nicolini D, Vivarelli M (2014) Liver transplantation in patients with common variable immunodeficiency: a report of two cases. Ann Transplant 19:541–544PubMedGoogle Scholar
  124. 124.
    Murakawa Y, Miyagawa-Hayashino A, Ogura Y, Egawa H, Okamoto S, Soejima Y, Kurosawa M et al (2012) Liver transplantation for severe hepatitis in patients with common variable immunodeficiency. Pediatr Transplant 16:E210–E216PubMedGoogle Scholar
  125. 125.
    Smith MS, Webster AD, Dhillon AP, Dusheiko G, Boulton R, Savage K, Rolles K et al (1995) Orthotopic liver transplantation for chronic hepatitis in two patients with common variable immunodeficiency. Gastroenterology 108:879–884PubMedGoogle Scholar
  126. 126.
    Rizzi M, Neumann C, Fielding AK, Marks R, Goldacker S, Thaventhiran J, Tarzi MD et al (2011) Outcome of allogeneic stem cell transplantation in adults with common variable immunodeficiency. J Allergy Clin Immunol 128:1371–1374.e1372PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017
corrected publication [March/2018]

Authors and Affiliations

  • Junmin Song
    • 1
    • 2
  • Ana Lleo
    • 3
  • Guo Xiang Yang
    • 1
  • Weici Zhang
    • 1
  • Christopher L. Bowlus
    • 4
  • M. Eric Gershwin
    • 1
  • Patrick S. C. Leung
    • 1
  1. 1.Division of Rheumatology/Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisUSA
  2. 2.Department of GastroenterologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  3. 3.Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research CenterMilanItaly
  4. 4.Division of Gastroenterology and HepatologyUniversity of CaliforniaDavisUSA

Personalised recommendations