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IgA anticardiolipin antibodies associated with Henoch-Schönlein purpura
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2 16. Wiklund DA, Weston WL. Incontinentia pigmenti: a fourgeneration study. Arch DermatoI1980;116:701-3. 17. Nazzaro V, Brusasco A, Gelmetti C, et al. Hypochromic reticulated streaks in incontinentia pigmenti: an immunohistochemical and ultrastructural study. Pediatr Dermatol 1990;7:174-8. 18. Mascaro JM, Palou J, Vives P. Painful subungual keratotic tumors in incontinentia pigmenti. JAM ACAD DERMATOL 1985;13:913-8. 19. Simmons DA, Kegel MF, Scher RK, et aL Subungual tumors in incontinentia pigmenti. Arch Dermatol 1986; 122: 1431-4. 20. Heathcote JG, Schoales BA, Willis NR. Incontinentia pigmenti (Bloch-Sulzberger syndrome): a case report and review of the ocular pathological features. Can J Ophthalmol 1991;26:229-37. 21. Rahi J, Hungerford J. Early diagnosis ofthe retinopathy of incontinentia pigmenti: successful treatment by cryotherapy. Br J Ophthalmol 1990;74:377-9.
Burden et al. 857 22. Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti. Am J OphthalmoI1990;110:701-2. 23. Damstra RJ, Van Duren JA, Van Ginkel CWJ. Incontinentia pigmenti (Bloch-Sulzberger). Br J Dermatol1991; 125:280-1. 24. Catalano, RA. Incontinentia pigmenti. Am J Ophthalmol 1990;110:696-9. 25. Roberts WM, Jenkins JJ, Moorhead EL, et aL Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer 1988;62:2370-2. 26. Menni S, Piccinno R, Biolchini A, et aL Immunologic investigations in eight patients with incontinentia pigmenti. Pediatr DermatoI1990;7:275-7. 27. Mallory SB, Krafchik BR. Incontinentia pigmenti: the syndrome page. Pediatr DermatoI1992;9:304-8.
IgA anticardiolipin antibodies associated with Henoch-Schonlein purpura A. David Burden, MRcp,a Ian W. Gibson, MBChB,b R. Stuart C. Rodger, FRCP,c and David M. Tillman, MRcpa Glasgow, Scotland Henoch-SchOnlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-SchOnlein purpura. A potential role for IgA autoantibodies in Henoch-SchOnlein purpura needs to be further explored. (J AM ACAD DERMATOL 1994;31:857-60.) Antiphospholipid antibodies are a heterogeneous group of immunoglobulins of the IgG, IgM, or IgA classes directed against a variety of phospholipid antigens. They are important risk factors for arterial and venous thrombosis and are also associated with recurrent fetal loss, thrombocytopenia, and an autoimmune postpartum syndrome. Various cutaneous manifestations have also been reported, such as
From the University of Glasgow Departments of Dennatology,' Pathology,b and Renal Medicine,c Western Infirmary. Reprint requests: A. David Burden, MRCP, University Department of Dermatology, Western Infirmary, Glasgow GIl 6NT, Scotland, United Kingdom. Copyright @ 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55289
livedo reticularis, 1 necrotizing purpura,2 and widespread cutaneous necrosis 3; these have recently been reviewed. 4 We report for the first time the finding of IgA anticardiolipin antibodies CACAs) in a patient with Henoch-Schonlein purpura CHSP). CASE REPORT A 51-year-old man had palpable purpura for 4 months on the legs (Fig. 1). Two years before he had a cerebrovascular accident that resulted in a right-sided hemiparesis. A computed tomographic scan at that time revealed infarction in the left middle cerebral artery territory. The patient had been taking low-dose aspirin since the cerebrovascular accident but was taking no other medication. His general health was otherwise good. In particular, he had no joint pains or abdominal symptoms and could recall no recent sore throat.
858 Burden et al.
J oumal of the American Academy of Dermatology November 1994
Direct immunofluorescence was negative for IgG, IgA, IgM, and C3. Heavy proteinuria (2 gmin 24 hours) was detected and urine microscopy revealed numerous red cells. Creatinine clearance was 130 ml/min, and a renal ultrasound result was normal. A renal biopsy specimen showed active glomerulonephritis of the focal segmental type in the absence of vasculitis. With immunofluorescence there was granular deposition of IgA (Fig. 3) and C3 in the capillary loops and mesangium.
DISCUSSION
Fig. 1. Purpuric eruption on legs.
His erythrocyte sedimentation rate and complete blood count were normal. The anti-streptolysin 0 titer was within the normal range and hepatitis B serologic study showed no abnormality. Antinuclear antibody was detected on one occasion but only at low titer (1:40, speckled pattern); anti-double-stranded DNA antibodies were not detected. Tests were negative for cryoglobulins, antiRo, La, Sm, and nRNP, for antineutrophil cytoplasmic antibody, including IgA antineutrophil cytoplasmic antibody, and for rheumatoid factor, including IgA rheumatoid factor. Serum IgA levels and complement were within the normal range. A standardized enzyme-linked immunosorbent assay for ACAs was performed as described by Loizou et al. 5 The normal range is 0 to 10 U 1m!. ACAs ofIgAserotype were detected, initially at a level of 18.8 U /ml, increasing after 4 months to 44 U /ml. Neither IgG nor IgM class ACAs were present. Screening tests for lupus anticoagulant, including the dilute Russel's viper venom time with a platelet neutralization step, were negative, as was the VDRL slide test. A skin biopsy specimen revealed a leukocytoclastic vasculitis of small vessels in the papillary dermis (Fig. 2).
The clinical diagnosis in this patient was considered to be HSP, on the basis of renal findings of IgA nephropathy and the presence of cutaneous Ieukocytoclastic vasculitis. Granular IgA has frequently been identified in the blood vessels of the papillary dermis of both affected and uninvolved skin in HSp.6 This is especially the case when the lesions are of recent onset. 7 The absence of IgA when the vasculitis has been present for 4 months (as in this patient) does not preclude the diagnosis of HSP. There is a spectrum of disease ranging from involvement restricted to the kidneys with IgA nephropathy (Berger's disease), to multisystem disease (HSP) in which vasculitis may affect the skin, joints, kidneys, and gastrointestinal tract. 8 In one study of HSP in adults, the full range of symptoms was present in only 19% of patients and involvement was limited to the skin and kidneys in 14%.9 Reports of focal neurologic deficits in HSP may be relevant to our patient. 10 These deficits are generally attributed to cerebral vasculitis but the presence of ACAs has not previously been addressed. ACAs may occur as an isolated clinical finding or in association with systemic disease, most notably systemic lupus erythematosus (SLE),l1 but also in other connective tissue diseases and in AIDS. 12 In addition, ACAs have been reported in Behget's disease,13 neoplasia, 14 and Degos' disease. 15 In patients with SLE there is no clear association between ACAs and renal lesions; indeed, some reports have suggested a protective effect of ACAs.16 McHugh et al., \7 however, suggested an association between renallesions and ACAs in a subgroup of patients with SLE who had livedo reticularis. The clinical relevance of the immunoglobulin isotype of ACAs remains largely unknown. Most studies of ACAs have looked for IgG and IgM isotypes; many laboratories do not routinely measure IgA antibodies. Nevertheless, IgA ACAs are known to occur rela-
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2
Burden et al. 859
Fig. 2. Skin biopsy specimen shows swollen endothelial cells, red cell extravasation, and perivascular neutrophil polymorphonuclear infiltrate with leukocytoclasia. (HematoxyJineosin stain; X250. Courtesy Dr. M. Fallowfield.)
Fig. 3. Renal biopsy specimen shows granular mesangial deposits of IgA on direct immunofluorescence (X400).
tively frequently in patients with SLE16 and, although IgG or IgM antibodies are often also present, IgA antibodies may occur alone. IS The pathogenesis of IgA nephropathy and HSP is not fully understood but involves the deposition of immune complexes in which most of the antibody is of the IgA class. 19 Secretory mucosae are considered
to be the primary source of the deposited IgA and there is some evidence of a general up-regulation of the IgA immune response. 20 The antigen component of the IgA immune complexes remains unclear; it is possible that different allergens are involved in different patients. Various exogenous antigens have been proposed, including infectious agents such as
Journal of the American Academy of Dermatology November 1994
860 Burden et at. cytomegalovirus21 and ingested agents22 such as gluten. 19A antibodies specific for endogenous components have also been demonstrated, most notably IgA rheumatoid factor 23 and IgA antineutrophil cytoplasmic antibody.24 To our knowledge, this is the first report of IgA A CAs in HSP, an association that has not previously been demonstrated, perhaps because IgA ACAs are not 'routinely measured in this condition. Funding for the cost of color reproductions was provided by Leo Laboratories Limited. REFERENCES 1. Asherson RA, Mayou SC, Merry P, et al. The spectrum of livedo reticularis and anticardiolinin antibodies. Br J DermatoI1989;120:215-21. . 2. Naldi L, Marchesi L, Finazzi G, et al. Antiphospholipid antibodies and necrotizing purpura. Dermatologica 1990; 180:272-5. 3. O'Neill A, Gatenby P A, McGaw B, et aI. Widespread cutaneous necrosis associated with cardiolipin antibodies. J AM ACAD DERMATOL 1990;22:356-9. 4. Stephens CJM. The antiphospholipid syndrome. Clinical correlations, mechanisms of thrombosis and treatment of patients with the lupus anticoagulant and anticardiolipin antibodies. Br J Dermatol 1991;125:199-210. 5. Loizou S, McCrea JD, Rudge AC, et al. Measurement of anticardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp ImmunoI1985;62:738-45. 6. Van Hale HM, Gibson LE, Schroeter AL. HenochSchOnlein vasculitis: direct immunofluorescence study of uninvolved skin. J AM ACAD DERMATOL 1986;15:665-70. 7. Logan W, Lynch P, Sams WM. Periodic synopsis on vasculitis. JAM ACAD DERMATOL 1985;12:716-7. 8. Waldo FB. Is Henoch-Schonlein purpura the systemic form of IgA nephropathy? Am J Kidney Dis 1988;12:373-7. 9. Cream JJ, Gumpel 1M, Peachey RDG. Schonlein-Henoch purpura in the adult. Q J Moo 1970;39:461-84. 10. Belman AL, Leicher CR, Mosche SL, et al. Neurologic manifestations of SchOnlein-Henoch purpura: report of
11. 12. 13.
14. 15. 16. 17.
18. 19. 20. 21. 22.
23.
24.
three cases and review of the literature. Pediatrics 1985; 75:687-92. Harris EN, Gharavi AE, Hughes GRV. Antiphospholipid antibodies. Coo Rheum Dis 1985;11:591-609. Bloom EJ, Abrams DI, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986; 256:491-3. Hull RG, Harris EN, Gharavi AE, et al. Anticardiolipin antibodies: occurrence in Beh'ict's syndrome. Ann Rheum Dis 1984;43:746-8. Schleider MA, Nachman RL, Jaffe EA, et al. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. Englert HJ, Hawkes CR, Boey ML, et al. Degos' disease: association with anticardiolipin antibodies and the lupus anticoagulant. BMJ 1984;289:576. Weidmann CE, Wallace DJ, Peter JB, et al. Studies ofIgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus. J Rheumatol 1988;15:74-9. McHugh NJ, Maymo J, Skinner RP, et al. Anticardiolipin antibodies, livedo reticularis and major cerebrovascular and renal disease in systemic lupus erythematosus. Ann Rheum Dis 1988;47:110-5. Gharavi AE, Harris EN, Asherson RA, et al. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987;46:1-6. Emancipator SN, Lamm ME. IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Lab Invest 1989;60:168-83. Clarkson AR, Woodroffe AJ, Bannister KM, et al. The syndrome ofIgA nephropathy. Clin N ephroI1984;2l:7-14. Gregory MC, Hammond ME, Brewer ED. Renal deposition of cytomegalovirus antigen in immunoglobulin A nephropathy. Lancet 1988;1:11-3. Sancho J, Egido J, Rivera F, et al. Immune complexes in IgA nephropathy: presence of antibodies against diet antigens and delayed clearance of specific polymeric IgA immune complexes. Coo Exp ImmunoI1983;54:l94-202. Czerkinsky C, Koopman WJ, Jackson S, et al. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangiaI immunoglobulin A nephropathies. J Clin Invest 1986;77:1931-8. Shaw G, Ronda N, Esnault V, et al. Anti neutrophil cytoplasmic antibodies (ANCA) of IgA class correlate with disease activity in adult Henoch-SchOnlein purpura. N ephrol Dial Transplant 1992;7:1238-41.
Burden et al. 857 22. Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti. Am J OphthalmoI1990;110:701-2. 23. Damstra RJ, Van Duren JA, Van Ginkel CWJ. Incontinentia pigmenti (Bloch-Sulzberger). Br J Dermatol1991; 125:280-1. 24. Catalano, RA. Incontinentia pigmenti. Am J Ophthalmol 1990;110:696-9. 25. Roberts WM, Jenkins JJ, Moorhead EL, et aL Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer 1988;62:2370-2. 26. Menni S, Piccinno R, Biolchini A, et aL Immunologic investigations in eight patients with incontinentia pigmenti. Pediatr DermatoI1990;7:275-7. 27. Mallory SB, Krafchik BR. Incontinentia pigmenti: the syndrome page. Pediatr DermatoI1992;9:304-8.
IgA anticardiolipin antibodies associated with Henoch-Schonlein purpura A. David Burden, MRcp,a Ian W. Gibson, MBChB,b R. Stuart C. Rodger, FRCP,c and David M. Tillman, MRcpa Glasgow, Scotland Henoch-SchOnlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-SchOnlein purpura. A potential role for IgA autoantibodies in Henoch-SchOnlein purpura needs to be further explored. (J AM ACAD DERMATOL 1994;31:857-60.) Antiphospholipid antibodies are a heterogeneous group of immunoglobulins of the IgG, IgM, or IgA classes directed against a variety of phospholipid antigens. They are important risk factors for arterial and venous thrombosis and are also associated with recurrent fetal loss, thrombocytopenia, and an autoimmune postpartum syndrome. Various cutaneous manifestations have also been reported, such as
From the University of Glasgow Departments of Dennatology,' Pathology,b and Renal Medicine,c Western Infirmary. Reprint requests: A. David Burden, MRCP, University Department of Dermatology, Western Infirmary, Glasgow GIl 6NT, Scotland, United Kingdom. Copyright @ 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55289
livedo reticularis, 1 necrotizing purpura,2 and widespread cutaneous necrosis 3; these have recently been reviewed. 4 We report for the first time the finding of IgA anticardiolipin antibodies CACAs) in a patient with Henoch-Schonlein purpura CHSP). CASE REPORT A 51-year-old man had palpable purpura for 4 months on the legs (Fig. 1). Two years before he had a cerebrovascular accident that resulted in a right-sided hemiparesis. A computed tomographic scan at that time revealed infarction in the left middle cerebral artery territory. The patient had been taking low-dose aspirin since the cerebrovascular accident but was taking no other medication. His general health was otherwise good. In particular, he had no joint pains or abdominal symptoms and could recall no recent sore throat.
858 Burden et al.
J oumal of the American Academy of Dermatology November 1994
Direct immunofluorescence was negative for IgG, IgA, IgM, and C3. Heavy proteinuria (2 gmin 24 hours) was detected and urine microscopy revealed numerous red cells. Creatinine clearance was 130 ml/min, and a renal ultrasound result was normal. A renal biopsy specimen showed active glomerulonephritis of the focal segmental type in the absence of vasculitis. With immunofluorescence there was granular deposition of IgA (Fig. 3) and C3 in the capillary loops and mesangium.
DISCUSSION
Fig. 1. Purpuric eruption on legs.
His erythrocyte sedimentation rate and complete blood count were normal. The anti-streptolysin 0 titer was within the normal range and hepatitis B serologic study showed no abnormality. Antinuclear antibody was detected on one occasion but only at low titer (1:40, speckled pattern); anti-double-stranded DNA antibodies were not detected. Tests were negative for cryoglobulins, antiRo, La, Sm, and nRNP, for antineutrophil cytoplasmic antibody, including IgA antineutrophil cytoplasmic antibody, and for rheumatoid factor, including IgA rheumatoid factor. Serum IgA levels and complement were within the normal range. A standardized enzyme-linked immunosorbent assay for ACAs was performed as described by Loizou et al. 5 The normal range is 0 to 10 U 1m!. ACAs ofIgAserotype were detected, initially at a level of 18.8 U /ml, increasing after 4 months to 44 U /ml. Neither IgG nor IgM class ACAs were present. Screening tests for lupus anticoagulant, including the dilute Russel's viper venom time with a platelet neutralization step, were negative, as was the VDRL slide test. A skin biopsy specimen revealed a leukocytoclastic vasculitis of small vessels in the papillary dermis (Fig. 2).
The clinical diagnosis in this patient was considered to be HSP, on the basis of renal findings of IgA nephropathy and the presence of cutaneous Ieukocytoclastic vasculitis. Granular IgA has frequently been identified in the blood vessels of the papillary dermis of both affected and uninvolved skin in HSp.6 This is especially the case when the lesions are of recent onset. 7 The absence of IgA when the vasculitis has been present for 4 months (as in this patient) does not preclude the diagnosis of HSP. There is a spectrum of disease ranging from involvement restricted to the kidneys with IgA nephropathy (Berger's disease), to multisystem disease (HSP) in which vasculitis may affect the skin, joints, kidneys, and gastrointestinal tract. 8 In one study of HSP in adults, the full range of symptoms was present in only 19% of patients and involvement was limited to the skin and kidneys in 14%.9 Reports of focal neurologic deficits in HSP may be relevant to our patient. 10 These deficits are generally attributed to cerebral vasculitis but the presence of ACAs has not previously been addressed. ACAs may occur as an isolated clinical finding or in association with systemic disease, most notably systemic lupus erythematosus (SLE),l1 but also in other connective tissue diseases and in AIDS. 12 In addition, ACAs have been reported in Behget's disease,13 neoplasia, 14 and Degos' disease. 15 In patients with SLE there is no clear association between ACAs and renal lesions; indeed, some reports have suggested a protective effect of ACAs.16 McHugh et al., \7 however, suggested an association between renallesions and ACAs in a subgroup of patients with SLE who had livedo reticularis. The clinical relevance of the immunoglobulin isotype of ACAs remains largely unknown. Most studies of ACAs have looked for IgG and IgM isotypes; many laboratories do not routinely measure IgA antibodies. Nevertheless, IgA ACAs are known to occur rela-
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2
Burden et al. 859
Fig. 2. Skin biopsy specimen shows swollen endothelial cells, red cell extravasation, and perivascular neutrophil polymorphonuclear infiltrate with leukocytoclasia. (HematoxyJineosin stain; X250. Courtesy Dr. M. Fallowfield.)
Fig. 3. Renal biopsy specimen shows granular mesangial deposits of IgA on direct immunofluorescence (X400).
tively frequently in patients with SLE16 and, although IgG or IgM antibodies are often also present, IgA antibodies may occur alone. IS The pathogenesis of IgA nephropathy and HSP is not fully understood but involves the deposition of immune complexes in which most of the antibody is of the IgA class. 19 Secretory mucosae are considered
to be the primary source of the deposited IgA and there is some evidence of a general up-regulation of the IgA immune response. 20 The antigen component of the IgA immune complexes remains unclear; it is possible that different allergens are involved in different patients. Various exogenous antigens have been proposed, including infectious agents such as
Journal of the American Academy of Dermatology November 1994
860 Burden et at. cytomegalovirus21 and ingested agents22 such as gluten. 19A antibodies specific for endogenous components have also been demonstrated, most notably IgA rheumatoid factor 23 and IgA antineutrophil cytoplasmic antibody.24 To our knowledge, this is the first report of IgA A CAs in HSP, an association that has not previously been demonstrated, perhaps because IgA ACAs are not 'routinely measured in this condition. Funding for the cost of color reproductions was provided by Leo Laboratories Limited. REFERENCES 1. Asherson RA, Mayou SC, Merry P, et al. The spectrum of livedo reticularis and anticardiolinin antibodies. Br J DermatoI1989;120:215-21. . 2. Naldi L, Marchesi L, Finazzi G, et al. Antiphospholipid antibodies and necrotizing purpura. Dermatologica 1990; 180:272-5. 3. O'Neill A, Gatenby P A, McGaw B, et aI. Widespread cutaneous necrosis associated with cardiolipin antibodies. J AM ACAD DERMATOL 1990;22:356-9. 4. Stephens CJM. The antiphospholipid syndrome. Clinical correlations, mechanisms of thrombosis and treatment of patients with the lupus anticoagulant and anticardiolipin antibodies. Br J Dermatol 1991;125:199-210. 5. Loizou S, McCrea JD, Rudge AC, et al. Measurement of anticardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results. Clin Exp ImmunoI1985;62:738-45. 6. Van Hale HM, Gibson LE, Schroeter AL. HenochSchOnlein vasculitis: direct immunofluorescence study of uninvolved skin. J AM ACAD DERMATOL 1986;15:665-70. 7. Logan W, Lynch P, Sams WM. Periodic synopsis on vasculitis. JAM ACAD DERMATOL 1985;12:716-7. 8. Waldo FB. Is Henoch-Schonlein purpura the systemic form of IgA nephropathy? Am J Kidney Dis 1988;12:373-7. 9. Cream JJ, Gumpel 1M, Peachey RDG. Schonlein-Henoch purpura in the adult. Q J Moo 1970;39:461-84. 10. Belman AL, Leicher CR, Mosche SL, et al. Neurologic manifestations of SchOnlein-Henoch purpura: report of
11. 12. 13.
14. 15. 16. 17.
18. 19. 20. 21. 22.
23.
24.
three cases and review of the literature. Pediatrics 1985; 75:687-92. Harris EN, Gharavi AE, Hughes GRV. Antiphospholipid antibodies. Coo Rheum Dis 1985;11:591-609. Bloom EJ, Abrams DI, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986; 256:491-3. Hull RG, Harris EN, Gharavi AE, et al. Anticardiolipin antibodies: occurrence in Beh'ict's syndrome. Ann Rheum Dis 1984;43:746-8. Schleider MA, Nachman RL, Jaffe EA, et al. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. Englert HJ, Hawkes CR, Boey ML, et al. Degos' disease: association with anticardiolipin antibodies and the lupus anticoagulant. BMJ 1984;289:576. Weidmann CE, Wallace DJ, Peter JB, et al. Studies ofIgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus. J Rheumatol 1988;15:74-9. McHugh NJ, Maymo J, Skinner RP, et al. Anticardiolipin antibodies, livedo reticularis and major cerebrovascular and renal disease in systemic lupus erythematosus. Ann Rheum Dis 1988;47:110-5. Gharavi AE, Harris EN, Asherson RA, et al. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987;46:1-6. Emancipator SN, Lamm ME. IgA nephropathy: pathogenesis of the most common form of glomerulonephritis. Lab Invest 1989;60:168-83. Clarkson AR, Woodroffe AJ, Bannister KM, et al. The syndrome ofIgA nephropathy. Clin N ephroI1984;2l:7-14. Gregory MC, Hammond ME, Brewer ED. Renal deposition of cytomegalovirus antigen in immunoglobulin A nephropathy. Lancet 1988;1:11-3. Sancho J, Egido J, Rivera F, et al. Immune complexes in IgA nephropathy: presence of antibodies against diet antigens and delayed clearance of specific polymeric IgA immune complexes. Coo Exp ImmunoI1983;54:l94-202. Czerkinsky C, Koopman WJ, Jackson S, et al. Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangiaI immunoglobulin A nephropathies. J Clin Invest 1986;77:1931-8. Shaw G, Ronda N, Esnault V, et al. Anti neutrophil cytoplasmic antibodies (ANCA) of IgA class correlate with disease activity in adult Henoch-SchOnlein purpura. N ephrol Dial Transplant 1992;7:1238-41.