Nephrol Dial Transplant (1992) 7: 952-955 © 1992 European Dialysis and Transplant Association-European Renal Association
Nephrology Dialysis Transplantation
Case Report IgA antimyeloperoxidase antibodies associated with crescentic IgA glomerulonephritis J. A. Savige and M. Gallicchio Department of Haematology, Repatriation General Hospital, Heidelberg, Victoria, Australia
Key words: IgA; ANCA; myeloperoxidase Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; PBS/T20, phosphate-buffered saline with Tween.
Introduction IgA glomerulonephritis is a common disease characterized by the demonstration of IgA and C 3 within the glomerular mesangium [1]. In severe cases IgA may be deposited along the glomerular capillary walls. Most evidence suggests that the glomerular mesangial damage results from the deposition of IgAcontaining immune complexes [2] and that these result either from overproduction of IgA or reduced clearance by the liver (although there there is now evidence that this may not be so) [3]. Increased IgA synthesis follows antigenic stimulation at mucosal surfaces after viral and bacterial infections [4]. In some cases of IgA glomerulonephritis, increased numbers of peripheral blood and tonsillar IgA-bearing lymphocytes, producing excessive IgA in vitro, as well as increased IgA-specific helper T and reduced IgA-specific suppressor T cell functions [5,6] have been noted. In addition IgA glomerulonephritis occurs when circulating IgA is not cleared adequately by the liver, and this condition is not uncommon in alcoholic liver disease. The target molecules of IgA antibodies have
been identified rarely, one exception being coeliac disease, where the IgA may be directed against gliadin [7]. The pathogenesis of IgA glomerulonephritis is still unclear but the recurrence of the disease after transplantation [8] suggests that the IgA molecule may be pathogenetic. pANCA are antineutrophil cytoplasmic antibodies usually demonstrated by indirect immunofluorescence to be directed against the perinuclear region of neutrophils and monocytes. They are directed against myeloperoxidase [9] elastase and other cytoplasmic constituents [10-12] and are commonly found in microscopic polyarteritis [9-13]. However, the pattern of glomerular immunoglobulin deposition is inconsistent [14] and a pathogenetic role for these antibodies is unclear. Here we describe a case where circulating IgA and lambda light-chain antimyeloperoxidase activity predominated in a case of IgA glomerulonephritis, and where the mesangial deposits were also IgA and lambda.
Subjects and methods Patient
A 33-year-old machinist with a past history of recurrent pneumothoraces and pleurodesis presented with episodic macroscopic haematuria and bilateral loin pain. There had been no immediate preceding respiratory infection and there were no clinical symptoms or signs indicative of a systemic vasculitis. Hb was 124 g/1, WCC 11.5 x 109/l and serum creatinine was 0.28 mmol/1, urea 12.9mmol/l, and 7 Correspondence and offprint requests to: Dr J. A. Savige, Depart- midstream urine specimen showed more than 10 glomerment of Medicine. Austin Hospital. Heidelberg. Victoria. Australia ular red blood cells, 20000 WBC, and 150 hyaline casts, hyaline casts with granules, RBC and WBC. Twenty-four 3081.
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IgA antimyeloperoxidase antibodies and IgA glomerulonephritis
hour urine collection contained 1.68 g of protein and the creatinine clearance was 0.3 mis. Antinuclear antibodies were not detected and anti-HBsAg antibodies were not present. Plasma IgA, IgG, and IgM were all within the normal range. The patient had a normal concentration of a!pha t antitrypsin. The renal biopsy contained 39 glomeruli, all of which were abnormal. There was a background of uneven diffuse mesangial proliferation but nearly 75% of the glomeruli at any given level showed focal proliferatke and necrotizing lesions, most of which were associated with significant crescent formation. About 10% of all the glomeruli showed extensive and occasionally circumferential crescents. There was abundant fibrin exudation and microthrombosis within the damaged capillaries together with a mononuclear and occasional polymorphonuclear inflammatory cell infiltrate. Small mesangial deposits were also seen. The basement membranes were regular with no significant protein deposits. There was mild interstitial oedema and early interstitial sclerosis with minimal interstitial inflammation. The tubules showed moderate diffuse atrophic changes and many contained fresh and partly lysed red blood cell casts. The interlobular vessels showed minimal intimal thickening with moderate muscular hypertrophy. On immunofluorescence there was moderate mesangial and coarsely granular capillary staining for IgA (Figure 1) and also for C 3 and lambda light chains. There was faint focal mesangial staining for IgG and IgM but not for C lq , or kappa light chains. The histological appearance was consistent with a diffuse proliferative and crescentic glomerulonephritis with immunofluoresence consistent with severe IgA glomerulonephritis. The patient was commenced on cyclophosphamide, warfarin, and prednisolone, and daily plasma exchanges for 5 days, followed by thrice-weekly exchanges. Two months later his serum creatinine was 0.16mmol/l but his urinary sediment remained active with more than 106 glomerular RBC/ml and 27 000 WBC/ml. A repeat renal biopsy showed diffuse moderate proliferative glomerulonephritis associated
953
with evidence of healing crescents and segmental proliferative lesions. No active crescent formation was seen. A repeat immunofluorescence examination was not performed. Cyclophosphamide, prednisolone, and plasma exchange were then stopped. Twenty-one months later his creatinine was 0.18 mmol,l, the urinary sediment showed 200000 glomerular RBC and his most recent renal biops> demonstrated diffuse necrotising crescentic glomerulonephritis with persisting activity and some healing. The IgA and lambda light chain immunofluorescence persisted in the later renal biopsy. The ELISA for the detection of IgG antimyeloperoxidase antibodies has been described in detail elsewhere [10]. The class and subclass of antimyeloperoxidase antibodies were investigated using polyclonal anti-rabbit anti-IgG 1/500 (Dako) and mouse monoclonal anti-human anti-IgA 1/5000, anti-IgM 1/5000, anti-kappa (1/10000) and antilambda (1/10000) light chains. The normal range for each of these was estimated by calculation of mean of 35 normal individuals plus 3 SD. The specificity of the IgA and lambda and kappa light chain antimyeloperoxidase binding activity was demonstrated with binding studies. Serum diluted 1/8 in PBS/T20 was assayed in ELISAs with increasing concentrations of myeloperoxidase using developing antisera for IgA and lambda and kappa light chains. An increase in serum binding to increasing concentrations of myeloperoxidase indicated that the antimyeloperoxidase activity was specific. Sera from seven other patients with crescentic IgA disease were also examined for IgA antimyeloperoxidase antibodies in the standard ELISA.
Results Serum from the patient described had IgG, IgA, and lambda and kappa light chain antimyeloperoxidase binding activity. The amount oflgG antimyeloperoxi-
Fig. I. Immunofluorescence micrograph of kidney section showing mesangial IgA and IgA in capillary walls (x960).
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954
dase bound was 46% (normal less than 30% = mean of 35 normal serum +4 SD) (Figure 1); IgA binding was 64% (normal less than 18%); lambda light chain activity 168% (normal less than 40%); and kappa light chain activity 51% (normal less than 18%). Most circulating activity thus resided in the IgA and lambda fractions although these results also reflect the affinity of the developing antibodies. The specificity of binding for myeloperoxidase was demonstrated by the increased binding of serum to increasing concentrations of myeloperoxidase on the ELISA plate. This is shown for IgA and lambda and kappa light chain activity (Figure 2A-C). None of another seven sera from patients with crescentic IgA glomerulonephritis bound at values greater than the normal range (less than 30% or 18%) in IgG or IgA antimyeloperoxidase ELISAs, indicating that antimyeloperoxidase binding activity is uncommon in IgA glomerulonephritis.
Discussion We have demonstrated here the presence of circulating IgA, IgG, and lambda and kappa light chains all specific for myeloperoxidase in a patient with segmental necrotizing glomerulonephritis and mesangial IgA and lambda light chain deposits. In this case the glomerular lesion was particularly aggressive, and linear IgA was present along the capillary walls. Antineutrophil cytoplasmic antibodies have been demonstrated in occasional cases of Henoch-Schonlein purpura [15], but in this case the antibodies showed specificity for myeloperoxidase and bound also to the vascular endothelium. This is the first indication that any antineutrophil cytoplasm antibody could bind to vascular endothelium in vivo; however, the nature of the binding is not clear. The glomerular lesions of IgA glomerulonephritis and segmental necrotizing glomerulonephritis arise from different mechanisms. In IgA disease the deposition of IgA results in local complement activation and polymorphonuclear infiltration and consequent injury. In contrast the mechanisms responsible for segmental necrotizing glomerulonephritis are unclear and the role of antineutrophil cytoplasmic antibodies is debated. However, one postulated mechanism involves intravascular activation of neutrophils. This has yet to be demonstrated in vivo. Antimyeloperoxidase antibodies are usually IgG in type and associated with a segmental necrotizing glomerulonephritis with variable or absent glomerular immune deposits. They have never been shown to bind to vascular endothelium and induce a vasculitis in vivo. Although IgA and lambda antimyeloperoxidase activity predominated, the presence of IgG and
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J. A. Savige and M. Gallicchio
Myetoperaddase (jjg/ni)
I 2 —•—
Pattern 1
--«--
Control
I Myetopercuddase (pg/ml)
Myetoperoxtdasa
Fig. 2. (A) IgA, (B) lambda, and (C) kappa light-chain antimyeloperoxidase activity (Q) compared with negative standard (O) and standard strongly positive in routine assay ( • ) . These all show an increase in binding of serum on plates with increased amounts of bound myeloperoxidase, indicating specificity of antimyeloperoxidase binding activity.
kappa light chain activity negated the possibility of a monoclonal antibody response. Thus IgA with other target specificities may have also been present in the circulation and in the kidney. However, the relative light chain subclass restriction makes it seem likely that some IgA and lambda light chain antimyeloperoxidase activity was present in the mesangial and capillary wall deposits. This specificity could have been proven if a glomerular eluate had been demonstrated to bind to myeloperoxidase or if kidney sections bound to fluoresceinated myeloperoxidase.
IgA antimyeloperoxidase antibodies and IgA glomerulonephritis
Although IgA antibodies are often associated with mucosal infections, and microscopic polyarteritis and Wegener's granulomatosis are often associated with a precipitating respiratory infection, one might expect more patients with IgA disease to have circulating IgA antimyeloperoxidase antibodies. However, we looked in a further seven patients and found that this was not the case. Furthermore there was no immediate antecedent respiratory infection in this patient, although there was a history of lung disease. Acknowledgements. This work was carried out with the help of the NH and MRC. We would like to thank the physicians who sent us the serum.
955
7.
8. 9.
10. 11. 12.
References 1. Berger J. IgA glomerular deposits in renal disease. Transplant Proc 1969; 1: 939 2. Emancipator S, Gallo G, Lamm M. IgA nephropathy: perspectives on pathogenesis and classification. Clin Nephrol 1985; 24: 161 3. Rifai A, Schena FP, Montinaro V el al. Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy. Lab Invest 1989; 61: 381-388 4. d'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 1987; 64: 709 5. Sakai H, Nomoto Y, Arimoro S. A decrease of IgA specific suppressor Tcell activity in patients with IgA nephropathy. Clin Exp Immunol 1979; 38: 243 6. Sakai H, Endoh M, Tomino Y, Nomoto Y. Increase of IgA
13.
14. 15.
specific T cells in patients with IgA nephropathy. Clin Exp Immunol 1982; 50: 77 Rostoker G, Pech M-A, Prata S el al. Serum IgG subclasses and IgM imbalances in adult IgA mesangial glomerulonephritis and idiopathic Hcnoch-Schonlein purpura. Clin Exp Immunol 1989; 75: 30-34 Berger J, Yaneva H, Nabara B, Barbanel C. Recurrence of mesangial deposition oflgA after renal transplantation. Kidney Int 1975; 7: 232 Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotising and crescentic glomerulonephritis. N Engl J Med 1988; 318: 1651 Gallicchio M, Savige JA. Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitides and infections. Clin Exp Immunol 1991; 84: 232-237 Falk RJ. ANCA-associated renal disease. Kidney Int 1990; 38: 998-1010 Goldschmeding R, Cohen Tervaert JW, van der Schoot CE, van der Veen, Kallenberg CGM, von dem Borne AEGK.. ANCA, anti-myeloperoxidase and anti-elastase; 3 members of a novel class of autoantibodies against myeloid lysosomal enzymes. In: Proceedings of the First International Workshop on ANCA, Copenhagen 1988. Ada Path Micro Immunol Scand 1989; 97: 48 Savage COS, Winearls CG, Jones S, Marshall PD, Lockwood CM. Prospective study of of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet 1987; 1: 1389-1393 Fauci AS, Wolff SM. Wegener's granulomatosis: studies in 18 patients and a review of the literature. Medicine (Baltimore) 1973; 52: 535 van der Wall Bake AWL, Lobatto S, Jonges L, Daha MR, van Es LA. IgA antibodies directed against cytoplasmic antigens of polymorphonuclear leucocytes in patients with Henoch-Schonlein purpura. Advances in Experimental Medicine and Biology. 1987; 216B
Received for publication 16.10.90 Accepted in revised form 29.12.91
Downloaded from https://academic.oup.com/ndt/article-abstract/7/9/952/1863015 by INSEAD user on 30 June 2018
Nephrology Dialysis Transplantation
Case Report IgA antimyeloperoxidase antibodies associated with crescentic IgA glomerulonephritis J. A. Savige and M. Gallicchio Department of Haematology, Repatriation General Hospital, Heidelberg, Victoria, Australia
Key words: IgA; ANCA; myeloperoxidase Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; PBS/T20, phosphate-buffered saline with Tween.
Introduction IgA glomerulonephritis is a common disease characterized by the demonstration of IgA and C 3 within the glomerular mesangium [1]. In severe cases IgA may be deposited along the glomerular capillary walls. Most evidence suggests that the glomerular mesangial damage results from the deposition of IgAcontaining immune complexes [2] and that these result either from overproduction of IgA or reduced clearance by the liver (although there there is now evidence that this may not be so) [3]. Increased IgA synthesis follows antigenic stimulation at mucosal surfaces after viral and bacterial infections [4]. In some cases of IgA glomerulonephritis, increased numbers of peripheral blood and tonsillar IgA-bearing lymphocytes, producing excessive IgA in vitro, as well as increased IgA-specific helper T and reduced IgA-specific suppressor T cell functions [5,6] have been noted. In addition IgA glomerulonephritis occurs when circulating IgA is not cleared adequately by the liver, and this condition is not uncommon in alcoholic liver disease. The target molecules of IgA antibodies have
been identified rarely, one exception being coeliac disease, where the IgA may be directed against gliadin [7]. The pathogenesis of IgA glomerulonephritis is still unclear but the recurrence of the disease after transplantation [8] suggests that the IgA molecule may be pathogenetic. pANCA are antineutrophil cytoplasmic antibodies usually demonstrated by indirect immunofluorescence to be directed against the perinuclear region of neutrophils and monocytes. They are directed against myeloperoxidase [9] elastase and other cytoplasmic constituents [10-12] and are commonly found in microscopic polyarteritis [9-13]. However, the pattern of glomerular immunoglobulin deposition is inconsistent [14] and a pathogenetic role for these antibodies is unclear. Here we describe a case where circulating IgA and lambda light-chain antimyeloperoxidase activity predominated in a case of IgA glomerulonephritis, and where the mesangial deposits were also IgA and lambda.
Subjects and methods Patient
A 33-year-old machinist with a past history of recurrent pneumothoraces and pleurodesis presented with episodic macroscopic haematuria and bilateral loin pain. There had been no immediate preceding respiratory infection and there were no clinical symptoms or signs indicative of a systemic vasculitis. Hb was 124 g/1, WCC 11.5 x 109/l and serum creatinine was 0.28 mmol/1, urea 12.9mmol/l, and 7 Correspondence and offprint requests to: Dr J. A. Savige, Depart- midstream urine specimen showed more than 10 glomerment of Medicine. Austin Hospital. Heidelberg. Victoria. Australia ular red blood cells, 20000 WBC, and 150 hyaline casts, hyaline casts with granules, RBC and WBC. Twenty-four 3081.
Downloaded from https://academic.oup.com/ndt/article-abstract/7/9/952/1863015 by INSEAD user on 30 June 2018
IgA antimyeloperoxidase antibodies and IgA glomerulonephritis
hour urine collection contained 1.68 g of protein and the creatinine clearance was 0.3 mis. Antinuclear antibodies were not detected and anti-HBsAg antibodies were not present. Plasma IgA, IgG, and IgM were all within the normal range. The patient had a normal concentration of a!pha t antitrypsin. The renal biopsy contained 39 glomeruli, all of which were abnormal. There was a background of uneven diffuse mesangial proliferation but nearly 75% of the glomeruli at any given level showed focal proliferatke and necrotizing lesions, most of which were associated with significant crescent formation. About 10% of all the glomeruli showed extensive and occasionally circumferential crescents. There was abundant fibrin exudation and microthrombosis within the damaged capillaries together with a mononuclear and occasional polymorphonuclear inflammatory cell infiltrate. Small mesangial deposits were also seen. The basement membranes were regular with no significant protein deposits. There was mild interstitial oedema and early interstitial sclerosis with minimal interstitial inflammation. The tubules showed moderate diffuse atrophic changes and many contained fresh and partly lysed red blood cell casts. The interlobular vessels showed minimal intimal thickening with moderate muscular hypertrophy. On immunofluorescence there was moderate mesangial and coarsely granular capillary staining for IgA (Figure 1) and also for C 3 and lambda light chains. There was faint focal mesangial staining for IgG and IgM but not for C lq , or kappa light chains. The histological appearance was consistent with a diffuse proliferative and crescentic glomerulonephritis with immunofluoresence consistent with severe IgA glomerulonephritis. The patient was commenced on cyclophosphamide, warfarin, and prednisolone, and daily plasma exchanges for 5 days, followed by thrice-weekly exchanges. Two months later his serum creatinine was 0.16mmol/l but his urinary sediment remained active with more than 106 glomerular RBC/ml and 27 000 WBC/ml. A repeat renal biopsy showed diffuse moderate proliferative glomerulonephritis associated
953
with evidence of healing crescents and segmental proliferative lesions. No active crescent formation was seen. A repeat immunofluorescence examination was not performed. Cyclophosphamide, prednisolone, and plasma exchange were then stopped. Twenty-one months later his creatinine was 0.18 mmol,l, the urinary sediment showed 200000 glomerular RBC and his most recent renal biops> demonstrated diffuse necrotising crescentic glomerulonephritis with persisting activity and some healing. The IgA and lambda light chain immunofluorescence persisted in the later renal biopsy. The ELISA for the detection of IgG antimyeloperoxidase antibodies has been described in detail elsewhere [10]. The class and subclass of antimyeloperoxidase antibodies were investigated using polyclonal anti-rabbit anti-IgG 1/500 (Dako) and mouse monoclonal anti-human anti-IgA 1/5000, anti-IgM 1/5000, anti-kappa (1/10000) and antilambda (1/10000) light chains. The normal range for each of these was estimated by calculation of mean of 35 normal individuals plus 3 SD. The specificity of the IgA and lambda and kappa light chain antimyeloperoxidase binding activity was demonstrated with binding studies. Serum diluted 1/8 in PBS/T20 was assayed in ELISAs with increasing concentrations of myeloperoxidase using developing antisera for IgA and lambda and kappa light chains. An increase in serum binding to increasing concentrations of myeloperoxidase indicated that the antimyeloperoxidase activity was specific. Sera from seven other patients with crescentic IgA disease were also examined for IgA antimyeloperoxidase antibodies in the standard ELISA.
Results Serum from the patient described had IgG, IgA, and lambda and kappa light chain antimyeloperoxidase binding activity. The amount oflgG antimyeloperoxi-
Fig. I. Immunofluorescence micrograph of kidney section showing mesangial IgA and IgA in capillary walls (x960).
Downloaded from https://academic.oup.com/ndt/article-abstract/7/9/952/1863015 by INSEAD user on 30 June 2018
954
dase bound was 46% (normal less than 30% = mean of 35 normal serum +4 SD) (Figure 1); IgA binding was 64% (normal less than 18%); lambda light chain activity 168% (normal less than 40%); and kappa light chain activity 51% (normal less than 18%). Most circulating activity thus resided in the IgA and lambda fractions although these results also reflect the affinity of the developing antibodies. The specificity of binding for myeloperoxidase was demonstrated by the increased binding of serum to increasing concentrations of myeloperoxidase on the ELISA plate. This is shown for IgA and lambda and kappa light chain activity (Figure 2A-C). None of another seven sera from patients with crescentic IgA glomerulonephritis bound at values greater than the normal range (less than 30% or 18%) in IgG or IgA antimyeloperoxidase ELISAs, indicating that antimyeloperoxidase binding activity is uncommon in IgA glomerulonephritis.
Discussion We have demonstrated here the presence of circulating IgA, IgG, and lambda and kappa light chains all specific for myeloperoxidase in a patient with segmental necrotizing glomerulonephritis and mesangial IgA and lambda light chain deposits. In this case the glomerular lesion was particularly aggressive, and linear IgA was present along the capillary walls. Antineutrophil cytoplasmic antibodies have been demonstrated in occasional cases of Henoch-Schonlein purpura [15], but in this case the antibodies showed specificity for myeloperoxidase and bound also to the vascular endothelium. This is the first indication that any antineutrophil cytoplasm antibody could bind to vascular endothelium in vivo; however, the nature of the binding is not clear. The glomerular lesions of IgA glomerulonephritis and segmental necrotizing glomerulonephritis arise from different mechanisms. In IgA disease the deposition of IgA results in local complement activation and polymorphonuclear infiltration and consequent injury. In contrast the mechanisms responsible for segmental necrotizing glomerulonephritis are unclear and the role of antineutrophil cytoplasmic antibodies is debated. However, one postulated mechanism involves intravascular activation of neutrophils. This has yet to be demonstrated in vivo. Antimyeloperoxidase antibodies are usually IgG in type and associated with a segmental necrotizing glomerulonephritis with variable or absent glomerular immune deposits. They have never been shown to bind to vascular endothelium and induce a vasculitis in vivo. Although IgA and lambda antimyeloperoxidase activity predominated, the presence of IgG and
Downloaded from https://academic.oup.com/ndt/article-abstract/7/9/952/1863015 by INSEAD user on 30 June 2018
J. A. Savige and M. Gallicchio
Myetoperaddase (jjg/ni)
I 2 —•—
Pattern 1
--«--
Control
I Myetopercuddase (pg/ml)
Myetoperoxtdasa
Fig. 2. (A) IgA, (B) lambda, and (C) kappa light-chain antimyeloperoxidase activity (Q) compared with negative standard (O) and standard strongly positive in routine assay ( • ) . These all show an increase in binding of serum on plates with increased amounts of bound myeloperoxidase, indicating specificity of antimyeloperoxidase binding activity.
kappa light chain activity negated the possibility of a monoclonal antibody response. Thus IgA with other target specificities may have also been present in the circulation and in the kidney. However, the relative light chain subclass restriction makes it seem likely that some IgA and lambda light chain antimyeloperoxidase activity was present in the mesangial and capillary wall deposits. This specificity could have been proven if a glomerular eluate had been demonstrated to bind to myeloperoxidase or if kidney sections bound to fluoresceinated myeloperoxidase.
IgA antimyeloperoxidase antibodies and IgA glomerulonephritis
Although IgA antibodies are often associated with mucosal infections, and microscopic polyarteritis and Wegener's granulomatosis are often associated with a precipitating respiratory infection, one might expect more patients with IgA disease to have circulating IgA antimyeloperoxidase antibodies. However, we looked in a further seven patients and found that this was not the case. Furthermore there was no immediate antecedent respiratory infection in this patient, although there was a history of lung disease. Acknowledgements. This work was carried out with the help of the NH and MRC. We would like to thank the physicians who sent us the serum.
955
7.
8. 9.
10. 11. 12.
References 1. Berger J. IgA glomerular deposits in renal disease. Transplant Proc 1969; 1: 939 2. Emancipator S, Gallo G, Lamm M. IgA nephropathy: perspectives on pathogenesis and classification. Clin Nephrol 1985; 24: 161 3. Rifai A, Schena FP, Montinaro V el al. Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy. Lab Invest 1989; 61: 381-388 4. d'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 1987; 64: 709 5. Sakai H, Nomoto Y, Arimoro S. A decrease of IgA specific suppressor Tcell activity in patients with IgA nephropathy. Clin Exp Immunol 1979; 38: 243 6. Sakai H, Endoh M, Tomino Y, Nomoto Y. Increase of IgA
13.
14. 15.
specific T cells in patients with IgA nephropathy. Clin Exp Immunol 1982; 50: 77 Rostoker G, Pech M-A, Prata S el al. Serum IgG subclasses and IgM imbalances in adult IgA mesangial glomerulonephritis and idiopathic Hcnoch-Schonlein purpura. Clin Exp Immunol 1989; 75: 30-34 Berger J, Yaneva H, Nabara B, Barbanel C. Recurrence of mesangial deposition oflgA after renal transplantation. Kidney Int 1975; 7: 232 Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotising and crescentic glomerulonephritis. N Engl J Med 1988; 318: 1651 Gallicchio M, Savige JA. Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitides and infections. Clin Exp Immunol 1991; 84: 232-237 Falk RJ. ANCA-associated renal disease. Kidney Int 1990; 38: 998-1010 Goldschmeding R, Cohen Tervaert JW, van der Schoot CE, van der Veen, Kallenberg CGM, von dem Borne AEGK.. ANCA, anti-myeloperoxidase and anti-elastase; 3 members of a novel class of autoantibodies against myeloid lysosomal enzymes. In: Proceedings of the First International Workshop on ANCA, Copenhagen 1988. Ada Path Micro Immunol Scand 1989; 97: 48 Savage COS, Winearls CG, Jones S, Marshall PD, Lockwood CM. Prospective study of of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet 1987; 1: 1389-1393 Fauci AS, Wolff SM. Wegener's granulomatosis: studies in 18 patients and a review of the literature. Medicine (Baltimore) 1973; 52: 535 van der Wall Bake AWL, Lobatto S, Jonges L, Daha MR, van Es LA. IgA antibodies directed against cytoplasmic antigens of polymorphonuclear leucocytes in patients with Henoch-Schonlein purpura. Advances in Experimental Medicine and Biology. 1987; 216B
Received for publication 16.10.90 Accepted in revised form 29.12.91
Downloaded from https://academic.oup.com/ndt/article-abstract/7/9/952/1863015 by INSEAD user on 30 June 2018
