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Archives of Dermatological Research

, Volume 299, Issue 5–6, pp 239–243 | Cite as

Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients: coincidental phenomenon with a risk of disease development?

  • Jolanta Dorota Torzecka
  • Katarzyna Woźniak
  • Cezary Kowalewski
  • Elżbieta Waszczykowska
  • Anna Sysa-Jedrzejowska
  • Hendri H. Pas
  • Joanna Narbutt
Original Paper

Abstract

Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was to assess the frequency of circulating IgG pemphigus autoantibodies in the healthy relatives of pemphigus patients and of their ability to bind in vivo in the epidermis. We also analyzed IgG subclasses distribution, both in the serum-positive relatives and in the patients. Our study included 67 healthy relatives, 50 healthy normal controls and 33 patients (25 at an active stage of the disease, 8 in clinical remission). To detect circulating pemphigus antibodies we applied indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The frequency of circulating pemphigus autoantibodies in the relatives, detected by IIF (30/67) was statistically higher (P < 0.001) than in the control group (0/50). ELISA revealed anti-desmoglein 1 and/or 3 antibodies in 13 out of 67 relatives. Direct immunofluorescence performed in 25 out of 32 seropositive relatives did not show intercellular bound in vivo IgG and/or C3 in the epidermis in any cases. Circulating IgG2 subclass was observed in 60% of the examined relatives and IgG4 was detected in 23.3% of them. In the patients at an active stage of pemphigus IgG4 and IgG1 were the dominant subclasses (96 and 76% relatively) while in clinical remission antibodies predominantly belonged to the IgG2 (75%) and IgG4 (37.5%) subclass. The obtained results confirmed polyclonal production of pemphigus autoantibodies and their different distributions dependent on the disease activity. Statistical analysis showed that the frequency of IgG1 and IgG4 subclasses was significantly higher in the patients at an active stage of the disease when compared to the patients in clinical remission (P < 0.001) or with seropositive healthy relatives (P < 0.001). The relevance of the presence of IgG4 autoantibodies in the healthy relatives’ sera requires further studies that focus on their potential pathogenicity.

Keywords

Pemphigus vulgaris Pemphigus foliaceus Healthy relatives Subclasses of IgG pemphigus autoantibodies 

Notes

Acknowledgments

Study was supported by scientific project of Polish Committee of Science (KBN no. 2P05B07727) and project of Medical University of Lodz (no. 503–1019–2).

References

  1. 1.
    Beutner EH, Jordon RE (1964) Demonstration of skin antibodies in sera of pemphigus vulgaris patients by indirect immunofluorescence staining. Proc Soc Exp Biol Med 117:505–510PubMedGoogle Scholar
  2. 2.
    Beutner EH, Hale WL, Nisengard RJ, Chorzelski TP, Holubar K (1973) Defined immunofluorescence in clinical immunopathology. In: Beutner EH, Chorzelski TP, Bean SF (eds) Immunopathology of the skin. Dowden Hutchinson and Ross, Pensylvania, pp 197–247Google Scholar
  3. 3.
    Bhol K, Natarajan K, Nagarwalla N, Mohimen A, Aoki V, Ahmed AR (1995) Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in pemphigus vulgaris: a model for autoimmunity. Proc Natl Acad Sci USA 92:5239–5243PubMedCrossRefGoogle Scholar
  4. 4.
    Brandsen R, Frusic-Zlotkin M, Lyubimov H, Yunes F Michel B, Tamir A, Milner Y, Brenner S (1997) Circulating pemphigus IgG in families of patients with pemphigus: comparison of indirect immunofluorescence, direct immunofluorescence, and immunoblotting. J Am Acad Dermatol 36:44–52PubMedCrossRefGoogle Scholar
  5. 5.
    Diaz LA, Arteaga LA, Hilario-Vargas J, Valenzuela JG, Li N, Warren S, Aoki V, Hans-Filho G, Eaton D, dos Santos V, Nutman TB, de Mayolo AA, Oaqish BF, Sampaio SA, Rivitti EA; Cooperative Group on Fogo Selvagem Research (2004) Anti-desmoglein–1 antibodies in onchocerciasis. leishmaniasis and Chagas diseas suggest a possible etiological link to Fogo selvagem. J Invest Dermatol 123:1045–1051Google Scholar
  6. 6.
    Edelson RL (2000) Pemphigus—decoding the cellular language of cutaneous autoimmunity. N Engl J Med 343:60–61PubMedCrossRefGoogle Scholar
  7. 7.
    Feinstein A, Yorav S, Movshovitz M, Schewach-Millet M (1991) Pemphigus in families. Int J Dermatol 30:347–351PubMedCrossRefGoogle Scholar
  8. 8.
    Futei Y, Amagai M, Ishii K, Kuroda-Kinoshita K, Ohya K, Nishikawa T (2001) Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus. J Dermatol Sci 26:55–61PubMedCrossRefGoogle Scholar
  9. 9.
    Harman KE, Gratian MJ, Seed PT, Bhogal BS, Challacombe SJ, Black MM (2000) Diagnosis pemphigus by ELISA: a critical evaluation of two ELISAs for the detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3. Clin Exp Dermatol 25:236–240PubMedCrossRefGoogle Scholar
  10. 10.
    Hertl M, Riechers R (2001) Autoreactive T cells as potential targets for immunotherapy of autoimmune bullous skin diseases. Clin Dermatol 19:592–597PubMedCrossRefGoogle Scholar
  11. 11.
    Hertl M, Veldman C (2001) Pemphigus—paradigm of autoantibody-mediated autoimmunity. Skin Pharmacol Appl Skin Physiol 14:408–418PubMedCrossRefGoogle Scholar
  12. 12.
    Jones CC, Hamilton RG, Jordon RE (1988) Subclass distribution of human IgG autoantibodies in pemphigus. J Clin Immunol 8:43–49PubMedCrossRefGoogle Scholar
  13. 13.
    Kim YH, Geoghegan WD, Jordon RE (1990) Pemphigus immunoglobulin G subclass autoantibodies: studies of reactivity with cultured human karatinocytes. J Lab Clin Med 115:324–331PubMedGoogle Scholar
  14. 14.
    Kricheli D, David M, Frusic-Zlotkin M, Goldsmith D, Rabinov M, Sulkes J, Milner Y (2000) The distribution of pemphigus vulgaris-IgG subclasses and their reactivity with desmoglein 3 and 1 in pemphigus patients and their first-degree relatives. Br J Dermatol 143:337–342PubMedCrossRefGoogle Scholar
  15. 15.
    Mohimen A, Narula M, Ruocco V, Pisani M, Ahmed AR (1993) Presence of the autoantibody in healthy relatives of Italian patients with pemphigus vulgaris. Arch Dermatol Res 285:176–177PubMedCrossRefGoogle Scholar
  16. 16.
    Nishikawa T (1999) Desmoglein ELISAs: a novel diagnostic tool for pemphigus. Arch Dermatol 135:195–196PubMedCrossRefGoogle Scholar
  17. 17.
    Ogawa MM, Hashimoto T, Nishikawa T, Castro RM (1989) IgG subclasses of intercellular antibodies in Brazilian pemphigus foliaceus—the relationship to complement fixing capability. Clin Exp Dermatol 14:29–31PubMedCrossRefGoogle Scholar
  18. 18.
    Rock B, Martins CR, Theofilopoulos AN, Balderas RS, Anhalt GJ, Labib RS, Futamura S, Rivitti EA, Diaz LA (1989) The pathogenic effect of IgG4 autoantibodies in endemic pemphigus foliaceus (fogo selvagem). N Engl J Med 320:1463–1469PubMedCrossRefGoogle Scholar
  19. 19.
    Sams WM, Schur PH (1973) Studies of the antibodies in pemphigoid and pemphigus. J Lab Clin Med 82:249–254PubMedGoogle Scholar
  20. 20.
    Sekiguchi M, Futei Y, Fujii Y, Iwaskai T, Nishikawa T, Amagai M (2001) Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive regions of desmogleins. J Immunol 167:5439–5448PubMedGoogle Scholar
  21. 21.
    Shirakata Y, Shiraishi S, Sayama K, Miki Y (1990) Subclass characteristics of IgG autoantibodies in bullous pemphigoid and pemphigus. J Dermatol 17:661–666PubMedGoogle Scholar
  22. 22.
    Tremeau-Martinage C, Oksman F, Bazex J (1995) Immunoglobulin G subclass distribution of anti-intercellular substance antibodies in pemphigus. Ann Dermatol Venereol 122:409–411PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jolanta Dorota Torzecka
    • 1
    • 3
  • Katarzyna Woźniak
    • 2
  • Cezary Kowalewski
    • 2
  • Elżbieta Waszczykowska
    • 1
  • Anna Sysa-Jedrzejowska
    • 3
  • Hendri H. Pas
    • 4
  • Joanna Narbutt
    • 3
  1. 1.Laboratory of Immunodermatology, Department of DermatologyMedical University of LodzLodzPoland
  2. 2.Department of DermatologyMedical University of WarsawWarsawPoland
  3. 3.Department of Dermatology and VenereologyMedical University of LodzLodzPoland
  4. 4.Center for Blistering DiseasesUniversity Hospital GroningenGroningenHolland

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