Advertisement

Journal of Clinical Immunology

, Volume 33, Issue 4, pp 865–870 | Cite as

Clinical, Immunological and Genetic Findings of a Large Tunisian Series of Major Histocompatibility Complex Class II Deficiency Patients

  • Imen Ben-Mustapha
  • Khaoula Ben-Farhat
  • Naouel Guirat-Dhouib
  • Emna Dhemaied
  • Beya Larguèche
  • Meriem Ben-Ali
  • Jalel Chemli
  • Jihène Bouguila
  • Lamia Ben-Mansour
  • Fethi Mellouli
  • Monia Khemiri
  • Mohamed Béjaoui
  • Mohamed-Ridha Barbouche
Brief Communication

Abstract

Introduction

Major histocompatibility complex class II (MHC-II) expression deficiency is a combined primary immunodeficiency leading to the impairment of the cellular and humoral immune responses. A majority of affected patients belong to consanguineous families particularly from the Maghreb, where a founder effect for a highly frequent mutation (named c.338-25_338del26) in the RFXANK gene was reported. Herein, we report the largest single Maghrebian country series of MHC-II deficient patients.

Patients and Methods

In Tunisia, among 551 PIDs diagnosed from 1993 to 2011, 54 had an MHC-II deficiency. The clinical features and immunological investigations were retrospectively analyzed in 34 children of them belonging to 28 kindred. The genetic study included the c.338-25_338del26 screening by the amplification of the affected region using polymerase chain reaction (PCR) followed by direct sequencing.

Results

Consanguinity was present in 22 out of 28 families. Mean age at the first infection was 6.1 months. Chronic diarrhea with failure to thrive and pulmonary infections were the most common manifestations occurring in 26 and 28 patients respectively. The most specific laboratory findings were the defect of MHC-II (HLA-DR) expression in all patients. The c.338-25_338del26 mutation was identified in 25 of them.

Conclusion

In Maghrebian settings, pediatricians should definitely consider this diagnosis in the presence of an early onset of severe and recurrent infections of the respiratory and intestinal tracts, particularly protracted diarrhea with a failure to thrive. The founder effect for the c.338-25_338del26 mutation in the RFXANK gene is also confirmed, facilitating prenatal diagnosis as a preventive approach in the Tunisian affected families with severe forms, particularly in the context of limited access to bone marrow transplantation.

Keywords

MHC-II deficiency primary immunodeficiency disease RFXANK gene Tunisia 

Notes

Acknowledgments

The authors would like to thank all of the patients and their families for their kind cooperation, as well as their physicians for the referrals.

References

  1. 1.
    Viret C, Janeway Jr CA. MHC and T cell development. Rev Immunogenet. 1999;1(1):91–104.PubMedGoogle Scholar
  2. 2.
    Cresswell P. Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol. 1994;12:259–93.PubMedCrossRefGoogle Scholar
  3. 3.
    Klein C, Lisowska-Grospierre B, LeDeist F, Fischer A, Griscelli C. Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome. J Pediatr. 1993;123(6):921–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M, et al. Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood. 2011;118(19):5108–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Reith W, Mach B. The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol. 2001;19:331–73.PubMedCrossRefGoogle Scholar
  6. 6.
    Rezaei N, Aghamohammadi A, Moin M, Pourpak Z, Movahedi M, Gharagozlou M, et al. Frequency and clinical manifestations of patients with primary immunodeficiency disorders in Iran: update from the Iranian Primary Immunodeficiency Registry. J Clin Immunol. 2006;26(6):519–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Al-Herz W, Alsmadi O, Melhem M, Recher M, Frugoni F, Notarangelo LD. Major Histocompatibility Complex Class II Deficiency in Kuwait: Clinical Manifestations, Immunological Findings and Molecular Profile. J Clin Immunol. 2012. [Epub ahead of print]Google Scholar
  8. 8.
    Reda SM, Afifi HM, Amine MM. Primary immunodeficiency diseases in Egyptian children: a single-center study. J Clin Immunol. 2009;29(3):343–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Naamane H, El Maataoui O, Ailal F, Barakat A, Bennani S, Najib J, et al. The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population. Eur J Pediatr. 2010;169(9):1069–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Djidjik R, Messaoudani N, Tahiat A, Meddour Y, Chaib S, Atek A, et al. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency. Allergy Asthma Clin Immunol. 2012;8(1):14.PubMedCrossRefGoogle Scholar
  11. 11.
    Steimle V, Otten LA, Zufferey M, Mach B. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome). Cell. 1993;75(1):135–46.PubMedGoogle Scholar
  12. 12.
    Masternak K, Barras E, Zufferey M, Conrad B, Corthals G, Aebersold R, et al. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. Nat Genet. 1998;20(3):273–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Steimle V, Durand B, Barras E, Zufferey M, Hadam MR, Mach B, et al. A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome). Genes Dev. 1995;9(9):1021–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Durand B, Sperisen P, Emery P, Barras E, Zufferey M, Mach B, et al. RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency. EMBO J. 1997;16(5):1045–55.PubMedCrossRefGoogle Scholar
  15. 15.
    Lisowska-Grospierre B, Fondaneche MC, Rols MP, Griscelli C, Fischer A. Two complementation groups account for most cases of inherited MHC class II deficiency. Hum Mol Genet. 1994;3(6):953–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Wiszniewski W, Fondaneche MC, Lambert N, Masternak K, Picard C, Notarangelo L, et al. Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B. Immunogenetics. 2000;51(4–5):261–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973–80.PubMedCrossRefGoogle Scholar
  18. 18.
    Le Deist F. [How should an immunodeficiency be explored?]. Arch Pediatr. 2003;10 Suppl 4:510s–2.PubMedCrossRefGoogle Scholar
  19. 19.
    Guirat-Dhouib N, Baccar Y, Mustapha IB, Ouederni M, Chouaibi S, El Fekih N, et al. Oral HPV infection and MHC class II deficiency (a study of two cases with atypical outcome). Clin Mol Allergy. 2012;10(1):6.PubMedCrossRefGoogle Scholar
  20. 20.
    BenMustapha-Darghouth I, Trabelsi S, Largueche B, Bejaoui M, Dellagi K, Barbouche MR. Prevalence of pneumocystis jiroveci pneumonia in Tunisian primary immunodeficient patients. Arch Pediatr. 2007;14(1):20–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Ben Abda I, Essid R, Mellouli F, Aoun K, Bejaoui M, Bouratbine A. Cryptosporidium infection in patients with major histocompatibility complex class II deficiency syndrome in Tunisia: description of five cases. Arch Pediatr. 2011;18(9):939–44.PubMedCrossRefGoogle Scholar
  22. 22.
    Halsey NA, Pinto J, Espinosa-Rosales F, Faure-Fontenla MA, da Silva E, Khan AJ, et al. Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil, and the United Kingdom. Bull World Health Organ. 2004;82(1):3–8.PubMedGoogle Scholar
  23. 23.
    Driss N, Ben-Mustapha I, Mellouli F, Ben Yahia A, Touzi H, Bejaoui M, et al. High susceptibility for enterovirus infection and virus excretion features in tunisian patients with primary immunodeficiencies. Clin Vaccine Immunol. 2012;19(10):1684–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Wiszniewski W, Fondaneche MC, Le Deist F, Kanariou M, Selz F, Brousse N, et al. Mutation in the class II trans-activator leading to a mild immunodeficiency. J Immunol. 2001;167(3):1787–94.PubMedGoogle Scholar
  25. 25.
    El Moncer W, Esteban E, Bahri R, Gaya-Vidal M, Carreras-Torres R, Athanasiadis G, et al. Mixed origin of the current Tunisian population from the analysis of Alu and Alu/STR compound systems. J Hum Genet. 2010;55(12):827–33.PubMedCrossRefGoogle Scholar
  26. 26.
    Barbouche MR, Galal N, Ben-Mustapha I, Jeddane L, Mellouli F, Ailal F, et al. Primary immunodeficiencies in highly consanguineous North African populations. Ann N Y Acad Sci. 2011;1238:42–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Imen Ben-Mustapha
    • 1
  • Khaoula Ben-Farhat
    • 2
  • Naouel Guirat-Dhouib
    • 3
  • Emna Dhemaied
    • 4
  • Beya Larguèche
    • 4
  • Meriem Ben-Ali
    • 2
  • Jalel Chemli
    • 5
  • Jihène Bouguila
    • 5
  • Lamia Ben-Mansour
    • 6
  • Fethi Mellouli
    • 3
  • Monia Khemiri
    • 7
  • Mohamed Béjaoui
    • 3
  • Mohamed-Ridha Barbouche
    • 1
  1. 1.Laboratoire de cyto-immunologie, LR11IPT02Institut Pasteur de TunisTunisTunisia
  2. 2.LR11IPT02Institut Pasteur de TunisTunisTunisia
  3. 3.Centre National de Greffe de Moelle OsseuseTunisTunisia
  4. 4.Laboratoire de cyto-immunologieInstitut Pasteur de TunisTunisTunisia
  5. 5.Service de PédiatrieCHU SahloulSousseTunisia
  6. 6.Service de pédiatrieCHU Hédi ChakerSfaxTunisia
  7. 7.Service de PédiatrieHôpital d’EnfantsTunisTunisia

Personalised recommendations