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Rheumatology 2001; 40: 111-112
© 2001 British Society for Rheumatology
Letters to the Editor |
Antiphospholipid antibody system in systemic sclerosis
DiSEM Section of Dermatology, University of Genoa, Viale Benedetto XV no. 7, 16132 Genoa and
1 Bouty s.p.a., Milan, Italy
SIR, Anti-phospholipid antibodies (aPLa) are a heterogeneous family of immunoglobulins directed to negatively charged phospholipids binding particular plasma proteins that behave as co-factors, e.g. ß 2 glycoprotein I (ß 2-GPI), prothrombin, protein C, protein S and annexin V. aPLa characterize the anti-phospholipid syndrome with thrombosis, thrombocytopenia and recurrent spontaneous abortions, but they can also be detected in connective tissue diseases, in particular systemic lupus erythematosus, and, more rarely, in lymphoproliferative disorders and infectious diseases such as syphilis, malaria, hepatitis A and mononucleosis. In infectious diseases, aPLa bind antigens in the absence of ß 2-GPI, which is required as a cofactor in autoimmune diseases [1]. In addition, thrombosis and thrombocytopenia can be associated with antibodies to ß 2-GPI alone.
The complete aPLa system has never been investigated in systemic sclerosis (SSc) [2–4]. Anticardiolipin antibodies (aCLa), usually studied in routine tests, have been found not to be associated with more severe ischaemia or other manifestations of the disease.
We aimed to confirm that SSc patients may present aPLa and to discover if antibodies to other phospholipids are present in addition to aCLa or in aCLa-negative patients. In addition, we investigated whether aPLa are associated with systemic involvement in the absence of venous or arterial thrombosis.
Ninety patients with SSc (86 females and four males) were classified according to LeRoy et al. [5] and blood-tested routinely.
Oesophageal motility and heart, lung and renal involvement were studied by conventional methods. Serological tests included antinuclear antibodies, anti-extractable nuclear antigens, anti-topoisomerase I (Scl70) antibodies and anti-centromere antibodies using indirect immunofluorescence and ELISA (Bouty, Milan, Italy). All sera were tested simultaneously for both IgG and IgM aPLa by a screening test (ELISA) in which the wells were coated with a mixture of cardiolipin, phosphatidyl serine, phosphatidyl inositol and phosphatidic acid, plus ß 2-GPI as cofactor (ORGen Tec, Mainz, Germany/Bouty). Sera that proved positive in the screening test were tested separately for both IgG and IgM antibodies to cardiolipin, phosphatidyl serine, phosphatidyl inositol and phosphatidic acid plus ß 2-GPI, and with the cofactor ß 2-GPI alone.
With the screening test, 14 patients (13 women and one man) proved to have antibodies directed to a mixture of phospholipids. Eleven patients (12.2%) (10 women and one man) had antibodies to a single phospholipid or to a combination of different phospholipids. Two of them had diffuse SSc (dSSc) and nine the limited form of SSc (lSSc). Four patients had anti Scl70 antibodies, six had anti-centromere and one anti-ribonucleoprotein antibodies (Table 1
).
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All aPLa-positive patients had IgG aCLa, three had anti-phosphatidyl serine, two anti-phosphatidyl inositol and two anti-phosphatidic acid antibodies. Three had anti-ß 2-GPI antibodies alone. Patients 2 and 3 also had IgM aPLa. The oesophagus was involved in eight patients, the lung in five and the kidney in one. None had the heart involved and none had a personal history of thrombotic complications. Seven patients had cutaneous ulcers (Table 2
).
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aCLa have been tested previously in SSc and found to be absent [3] or present in 30% of cases [2, 4] no matter how severe the disease. We confirmed that about 12% of SSc patients had aCLa belonging mainly to the IgG class. Antibodies to other phospholipids, however, were also present occasionally (Table 1
).
In our patients, the behaviour of aPLa other than classical aCLa differed from that in systemic lupus erythematosus. In the latter, in the absence of aCLa, thrombotic episodes are associated with anti-phosphatidyl serine plus ß 2-GPI and anti-phosphatidyl-inositol plus ß 2-GPI antibodies [6]. In our patients, however, aPLa other than aCLa were not detected alone and were not associated with a history of either thrombosis or recurrent abortions. The mother of patient 11 (Table 1) had multiple thrombosis and her daughter had an anti-phospholipid syndrome with recurrent abortions.
Two of our aPLa-positive patients also had antibodies of the IgM class. Usually IgG is the most prevalent isotype among patients with thrombosis and fetal loss, but clinical features of anti-phospholipid syndrome have been found associated with IgM and even IgA isotypes.
Visceral involvement in our aPLa-positive patients was not severe. Cutaneous ulcers were more frequent (63% vs 39% in aPLa-negative patients). In our aPLa-negative patients, instead, the heart was involved more frequently than in aPLa-positive patients.
In conclusion, the role of aPLa in SSc patients remains unknown, but their presence seems to be irrelevant as far as systemic involvement is concerned.
Notes
References
- Graves M. Antiphospholipid antibodies and thrombosis. Lancet1999;353:1348–53.[ISI][Medline]
- Katayama I, Otoyama K, Kondo S et al. Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic sclerosis. J Am Acad Dermatol1990;23:198–201.[ISI][Medline]
- Fonollosa V, Selva A, Lima J et al. Anticardiolipin antibodies in systemic sclerosis. J Am Acad Dermatol1991;25:133–4.[Medline]
- Herrick AL, Heaney M, Hollis S, Jayson MIV. Anticardiolipin, anticentromere and anti Scl 70 antibodies in patients with systemic sclerosis and severe digital ischaemia. Ann Rheum Dis1994;53:540–2.
[Abstract/Free Full Text] - Le Roy EC, Black C, Fleischmajer R et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol1988;15:202–5.[ISI][Medline]
- Barkas NE. Phospholipid autoantibodies. Phosphatidylserine. In: Peter JB, Shoenfeld Y, ed. Autoantibodies. Amsterdam: Elsevier Science, 1996:630–4.
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