Skip to main content

Advertisement

Log in

Detection of 16α-Hydroxyestrone-histone 1 Adduct as High-Affinity Antigen for Rheumatoid Arthritis Autoantibodies

  • Original Article
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Increased concentrations of 16α-hydroxyestrone (16α-OHE1) have been observed in rheumatoid arthritis (RA), but the underlying mechanism of this remains elusive. Here we aimed to identify the role played by 16α-OHE1 in RA. In 40 RA patients, the specificities of antibodies from the sera of these patients were checked by direct binding, inhibition ELISA, and quantitative precipitation titration. Competition ELISA was also used for the estimation of 16α-OHE1 in the serum of different RA patients. RA IgG from a patient’s sera showed strong recognition to 16α-OHE1-H1 (histone 1) adduct in comparison to control subjects (p < 0.001), as the formation of this adduct brings out various biochemical changes that might generate neo-epitopes, which have been well-recognized by these antibodies. The affinity of RA antibodies for 16α-OHE1-H1 (1.10 × 10− 7 M) was high, as detected by the Langmuir plot. Comparing RA patients to the controls, no significant differences were detected in the level of 16α-OHE1 or 2-hydroxyestrone/16α-OHE1 ratio. 16α-OHE1-H1 might have an antigenic role and function as a high-affinity antigen for RA autoantibodies and, therefore, could be used as a biomarker for this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aitcheson CT, Peebles C, Joslin F et al (1980) Characteristics of antinuclear antibodies in rheumatoid arthritis. Arthritis Rheum 23:528–538

    Article  CAS  Google Scholar 

  • Arnett FC, Edworthy TA, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for quantitation of micrograms quantity of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Castagnetta L, Carruba G, Granata OM et al (2003) Increased estrogen formation and estrogen to androgen ratio in the SF of patients with rheumatoid arthritis. J Rheumatol 30:2597–2605

    PubMed  CAS  Google Scholar 

  • Cutolo M, Capellino S, Montagna P et al (2003) New role of estrogen in rheumatoid arthritis. Clin Exp Rheumatol 21:687–690

    PubMed  CAS  Google Scholar 

  • Cutolo M, Sulli A, Straub RH (2012) Estrogen metabolism and autoimmunity. Autoimmun Rev 11:A460–A464

    Article  CAS  Google Scholar 

  • Enzinger J (1954) [Urinary estrogen excretion in polyarthritis]. Wien Z Inn Med 35:42–45

    PubMed  CAS  Google Scholar 

  • George J, Shoenfeld Y (1996) Natural autoantibodies. In: Peter JB, Shoenfeld Y (eds) Autoantibody. Elsevier Scientific, Amsterdam, pp 534–539

    Chapter  Google Scholar 

  • Goding JW (1978) Use of staphylococcal protein-A as immunological reagent. J Immunol Methods 20:241–254

    Article  CAS  Google Scholar 

  • Khan WA, Assiri AS (2011) Immunochemical studies on catecholestrogen modified plasmid: Possible role in rheumatoid arthritis. J Clin Immunol 31:22–29

    Article  CAS  Google Scholar 

  • Khan WA, Qureshi JA (2015) Increased binding of circulating systemic lupus erythematosus autoantibodies to recombinant interferon alpha 2b. APMIS 123:1016–1024

    Article  CAS  Google Scholar 

  • Khan WA, Habib S, Khan WA et al (2008) Enhanced binding of circulating SLE autoantibodies to Catecholestrogen-copper-modified DNA. Mol Cell Biochem 315:143–150

    Article  CAS  Google Scholar 

  • Kuiper S, van Gestel AM, Swinkels HL et al (2001) Influence of sex, age, and menopausal state on the course of early rheumatoid arthritis. J Rheumatol 28:1809–1816

    PubMed  CAS  Google Scholar 

  • Lahita RG (1996) The connective tissue diseases and the overall influence of gender. Int J Fertil Menopausal Stud 41:156–160

    PubMed  CAS  Google Scholar 

  • Lahita RG, Bradlow HL, Kunkel HG et al (1979) Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum 22:1195–1198

    Article  CAS  Google Scholar 

  • Lahita RG, Bradlow HL, Kunkel HG et al (1981) Increased 16 α-hydroxylation of estradiol in systemic lupus erythematosus. J Clin Endocrinol Metab 53:174–178

    Article  CAS  Google Scholar 

  • Langumir I (1918) The adsorption of gas on plane surface glass, mica and platinum. J Am Chem Soc 40:1361–1403

    Article  Google Scholar 

  • Morgan K, Clague RB, Collins I et al (1987) Incidence of antibodies to native and denatured cartilage collagens (types II, IX and XI) and to type I collagen in rheumatoid arthritis. Ann Rheum Dis 46:902–907

    Article  CAS  Google Scholar 

  • Pauls JD, Silverman E, Laxer RM et al (1989) Antibodies to histone H1 and H5 in the sera of patients with juvenile rheumatoid arthritis. Arthritis Rheum 32:877–883

    PubMed  CAS  Google Scholar 

  • Schmidt M, Hartung R, Capellino S et al (2009) Estrone/17 β-estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patient with rheumatoid arthritis and patient with osteoarthritis. Arthritis Rheum 60:2913–2922

    Article  CAS  Google Scholar 

  • Schneider J, Huh MM, Bradlow HL et al (1984) Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells. J Biol Chem 259:4840–4845

    PubMed  CAS  Google Scholar 

  • Seriolo B, Cutolo M, Garnero A et al (1999) Relationships between serum 17-oestradiol and anticardiolipin antibody concentrations in female patients with rheumatoid arthritis. Rheumatology 38:1159–1161

    Article  CAS  Google Scholar 

  • Steiner G, Smolen J (2002) Autoantibodies in rheumatoid arthritis and their clinical significance. Arthritis Res 4(suppl 2):S1–S5

    Article  Google Scholar 

  • Straub RH (2007) The complex role of estrogen in inflammation. Endocr Rev 28:521–574

    Article  CAS  Google Scholar 

  • Tengstrand B, Ahlmen M, Hafstrom I (2004) The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years. J Rheumatol 31:214–222

    PubMed  Google Scholar 

  • Weidler C, Harle P, Schedel J et al (2004) Patients with rheumatoid arthritis and systemic lupus erythematosus have increased renal excretion of mitogenic estrogens in relation to endogenous antiestrogens. J Rheumatol 31:489–494

    PubMed  CAS  Google Scholar 

  • Yu SC, Fishman J (1985) Interaction of histone with estrogen. Covalent adduct formation with 16 α-hydroxyestrone. Biochemistry 24:8017–8021

    Article  CAS  Google Scholar 

  • Zutshi DW, Reading CA, Epstein WV et al (1969) FII haemagglutination test for serum antigammaglobulin factor in arthritides sero-positive and sero-negative by other test. Ann Rheum Dis 28:289–299

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant (No. 246) from Deanship of Scientific Research, King Khalid University, Abha, Kingdom of Saudi Arabia.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wahid Ali Khan.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, W.A., Zaman, G.S. Detection of 16α-Hydroxyestrone-histone 1 Adduct as High-Affinity Antigen for Rheumatoid Arthritis Autoantibodies. Arch. Immunol. Ther. Exp. 66, 379–388 (2018). https://doi.org/10.1007/s00005-018-0512-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-018-0512-z

Keywords

Navigation