Summary
Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism that results from a deficiency of the lysosomal enzyme α-galactosidase A. This defect leads to the accumulation of its substrates, mainly globotriaosylceramide, in lysosomes of cells of different tissues. Different studies have shown the involvement of immunopathologies in different sphingolipidoses. The coexistence of FD and immune disorders such as systemic lupus erythematosus, rheumatoid arthritis and IgA nephropathy, has been described in the literature. The aim of this study was to evaluate the prevalence of a group of autoantibodies in a series of Argentine FD patients. Autoantibodies against extractable nuclear antigens (ENAs), double-stranded DNA, anticardiolipin and phosphatidylserine were assayed by ELISA. Lupus anticoagulants were also tested. Fifty-seven per cent of the samples showed reactivity with at least one autoantigen. Such reactivities were more frequent among males than among females. Antiphospholipid autoantibodies were detected in 45% of our patients. The high rate of thrombosis associated with FD could be related, at least in part, to the presence of antiphospholipid autoantibodies in Fabry patients. We found the presence of ENAs, which are a characteristic finding of rheumatological diseases, previous a frequent misdiagnosis of FD, in around 39% of the cases. The detection of a high level of autoantibodies must be correlated clinically to determine the existence of an underlying autoimmune disease. With the recent development of therapy, the life expectancy in FD will increase and autoimmune diseases might play an important role in the morbidity of FD.
Similar content being viewed by others
Abbreviations
- CL:
-
cardiolipin
- dsDNA:
-
double-stranded DNA
- ENAs:
-
extractable nuclear antigens
- FD:
-
Fabry disease
- LA:
-
lupus anticoagulant
- PS:
-
phosphatidylserine
References
Arias Martinez N, Barbado Hernandez FJ, Perez Martin G, Perez de Ayala C, Casal Esteban V, Vazquez Rodriguez JJ (2003) Fabry’s disease associated with rheumatoid arthritis. Multisystemic crossroads. An Med Interna 20: 28–30.
Beeson PB (1994) Age and sex associations of 40 autoimmune diseases. Am J Med 96: 457–462.
Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L (1967) Enzymatic defect in Fabry disease. N Engl J Med 276: 1163–1167.
Burstein Y, Rechavi G, Rausen AR, Frisch B, Spirer Z (1985) Association of Gaucher’s disease and lymphoid malignancy in 2 children. Scand J Haematol 35: 445–447.
Cines DB, McCrae KR (1995) The antiphospholipid-protein syndrome. J Clin Immunol 15: 86S–100S.
Costello R, O’Callaghan T, Sebahoun G (2006) Gaucher disease and multiple myeloma. Leuk Lymphoma 47: 1365–1368.
Desnick RJ, Ioannou YA, Eng CM (1995) α-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly WX, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill, 2741–2784.
Eitzman DT, Bodary PF, Shen Y, et al (2003) Fabry disease in mice is associated with age-dependent susceptibility to vascular thrombosis. J Am Soc Nephrol 14: 298–302.
Fox H, McCarthy P, Andre-Schwartz J, Shoenfeld Y, Miller K.B (1984) Gaucher’s disease and chronic lymphocytic leukemia. Possible pathogenetic link between Gaucher’s disease and B-cell proliferations? Cancer 54: 312–314.
Hamers MN, Donker-Koopman WE, Coulon-Morelec MJ, Dupouey P, Tager JM (1978) Characterization of antibodies and globoside. Immunochemistry 15: 353–358.
Kint JA (1970) Fabry disease. Alpha galactosidase deficiency. Science 167: 1268–1269.
Lahita RG (1996) The connective tissue diseases and the overall influence of gender. Int J Fertil Menopausal Stud 41: 156–165.
Leslie RD, Hawa M (1994) Twin studies in auto-immune disease. Acta Genet Med Gemellol 43: 71–81.
Marie JP, Tulliez M, Tricottet-Paczinski V, Reynes M, Diebold J (1982) Gaucher’s disease with monoclonal gammopathy. Significance of splenic plasmacytosis. Scand J Haematol 28: 54–58.
Marti GE, Ryan ET, Papadopoulos NM, et al (1988) Polyclonal B-cell lymphocytosis and hypergammaglobulinemia in patients with Gaucher disease. Am J Hematol 29: 189–194.
McDermot KD, Holmes A, Miners AH (2001) Anderson–Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 38: 750–760.
Meikle PJ, Ranieri E, Ravenscroft EM, Hua CT, Brooks DA, Hopwood JJ (1999) Prevalence of lysosomal storage disorders. JAMA 281: 249–254.
Mehta A, Ricci R, Widmer U, et al (2004) Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34: 236–242
Mizukami H, Mi Y, Wada R, et al (2002) Systemic inflammation in glucocerebroside-deficient mice with minimal glucosylceramide storage. J Clin Invest 109: 1215–1221.
Rahman P, Gladman DD, Wither J, Silver MD (1998) Coexistence of Fabry’s disease and systemic lupus erythematosus. Clin Exp Rheumatol 16: 475–478.
Rosenmann E, Kobrin I, Cohen T (1983) Kidney involvement in systemic lupus erythematosus and Fabry’s disease. Nephron 34: 180–184.
Sanchez-Guerrero J, Lew RA, Fossel AH, Schur PH. (1996) Utility of anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus. Arthritis Rheum 39: 1055–1061.
Simmelink MJA, Horbach DA, Derksen RHWM, et al (2001) Complexes of antiprothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. Br J Haematol 113: 621–629.
Soloninka CA, Laskin CA, Wither J, Wong D, Bombardier C, Raboud J (1991) Clinical utility and specificity of anticardiolipin antibodies. J Rheumatol 18: 1849–1855.
Utsumi K, Yamamoto N, Kase R (1997) High incidence of thrombosis in Fabry’s disease. Intern Med 36: 327–329.
Whybra C, Kampmann C, Willers I (2001) Anderson–Fabry disease: clinical manifestations of disease in female heterozygotes. J Inherit Metab Dis 24: 715–724.
Whybra C, Schwarting A, Kriegsmann J, et al (2006) IgA nephropathy in two adolescent sisters heterozygous for Fabry disease. Pediatr Nephrol 21: 1251–1256.
Yamaguchi A, Katsuyama K, Nagahama K, Takai T, Aoki I, Yamanaka S (2004) Possible role of autoantibodies in the pathophysiology of GM2 gangliosides. J Clin Invest 113: 200–208.
Zhao Y, Rumold R, Zhu M, et al (1999) An IgG antiprothrombin antibody enhances prothrombin binding to damaged endothelial cells and shortens plasma coagulation times. Arthritis Rheum 42: 2132–2138.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicating editor: Joe Clarke
Competing interests: None declared
References to electronic databases: Fabry disease (FD), OMIM 301500. α-Galactosidase A (α-D-galactoside galactohydrolase), EC 3.2.1.22.
Rights and permissions
About this article
Cite this article
Martinez, P., Aggio, M. & Rozenfeld, P. High incidence of autoantibodies in Fabry disease patients. J Inherit Metab Dis 30, 365–369 (2007). https://doi.org/10.1007/s10545-007-0513-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10545-007-0513-2