Pathologic findings in mesangiopathic glomerulonephritis in Navajo Indians

Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.     

Immunoglobulin and complement deposition in glomeruli of 756 subjects who had committed suicide or met with a violent death.

AIMS--To study immune deposits in renal glomeruli. METHODS--Tissue was obtained from 756 necropsy cases from people who had committed suicide or met with a violent death. Glomerular immune deposits were examined by immunofluorescence microscopy and a light microscopy. The clinical histories of all the decreased were studied to ascertain reasons for the deposits. RESULTS--Immune deposits were found in glomeruli in 91 (12%) cases. In 52 (6.8%) cases mesangial IgA was observed as a solitary finding in 34 (4.5%), and was accompanied by other immunoglobulins in 18 (2.4%). Mesangial IgM was present in 19 (2.5%) and IgG in 11 cases (1.5%). Two cases had capillary IgG (0.3%). Light microscopic examination showed mesangial enlargement in eight of the cases with mesangial IgA. These included one with IgA glomerulonephritis diagnosed before death. Two cases with normal glomerular morphology and mesangial IgA deposits had clinical laboratory evidence of renal disease. In two subjects with normal glomerular morphology, mesangial IgM and microscopic haematuria were present. In one case with capillary IgG membranous glomerulonephritis was detected. CONCLUSIONS--Ten cases had mesangial IgA together with morphological or clinical laboratory findings suggestive of renal disease. If all these are regarded as IgA glomerulonephritis, then its prevalence can be estimated at 1.3%. For IgM glomerulonephritis, a prevalence of 0.3% was deduced.     

Treponemal antigen in immunopathogenesis of syphilitic glomerulonephritis.

A patient with syphilitic glomerulonephritis had a renal biopsy and was treated for secondary syphilis. Light, electron, and immunofluorescence microscopic studies revealed an acute proliferative glomerulonephritis with subepithelial, intramembranous, and subendothelial immune complex deposits containing IgG, IgA, IgM, C4, and C3. Similar local deposits containing predominantly IgM were noted in areas of mesangial proliferation. Indirect fluorescent antibody studies employing rabbit treponemal antibody and sheep antirabbit globulin conjugate revealed the presence of treponemal antigen in the glomerular deposits. This finding provides strong evidence for the immunopathogenesis of the glomerular lesion as well as a causal link with Treponema pallidum.     

Experimental glomerulonephritis in the mouse associated with mesangial deposition ofautologous ferritin immune complexes.

Mice undergoing prolonged (5 to 8 weeks) immunization with cadium-free feeritin were studied 1 to 32 days following the last ferritin injection. Urine protein was measured and renal tissue examined by light, immunofluorescence, and electron microscopy. Immunized animals developed significant proteinuria and circulating antibody to ferritin.by light microscopy, proetinuric animals had a proliferative glomerular lesion with mesangial hypercellularity and martrix increase, focal and segmental necrosis, fibrin deposits, and occasional crescents. Iron stains revealed prominent mesangial iron deposition. In immunized animals, IgG and C3 deposits were localized mainly in the mesanglium. Electron microscopic studies revealed marked deposition of ferratin complexesexpanded mesangial matrix and mesangial interposition. Ferratin immune complexes were also visualized in epithelial spaces. In the latter location ferritin immune complexes occasionally formed characteristic electron-dense subepithelial deposits. In this model, mesangial and subepithelial localization of autologous ferritin immune complexes is associated with development of glomerulonephritis and characteristic mesangial lesions resembling those seen in some types of human glomerulonephritis.     

Morphology of IgA nephritis (Berger disease). Immunohistologic, light- and electron microscopic findings

An IgA nephritis was diagnosed in 109 (24%) out of 445 renal biopsies with glomerular disease in the years from 1977 to 1985. The mean age of the patients in question was 29 years. The male:female sex ratio was 2.6:1. Immunohistologically, the characteristic branching mesangial IgA deposits were uniformly present. In addition 96% showed mesangial C3 and 54% mesangial IgG and/or IgM deposits. Besides, immunoglobulin and/or C3 deposits could be detected at glomerular basement membranes (20%). The histological types of IgA nephritis were minor glomerular abnormalities (10%), focal/segmental glomerulonephritis (29%), diffuse mesangioproliferative (58%), membranoproliferative (1 case), and sclerosing glomerulonephritis (2 cases). Additional tubulointerstitial lesions were found in 55%. Electron microscopically, in 53 cases under study, mesangial electron dense immunodeposits were seen. At the glomerular basement membranes, deposits could be found only in 23 examined cases (43%). The comparison of clinical data with morphological findings showed relationships between the degree of proteinuria and creatinine level increase with the histological type of IgA nephritis and with the degree of glomerular sclerosis, tubulointerstitial lesions, and electron microscopically proved glomerular basement membrane deposits. Hematuria seemed not to correlate with the morphological picture.     

Interstrain variations in nephritogenicity of heterologous protein in mice

Swiss albino, BALB/c, and eight substrains of C3H mice were given daily intraperitoneal injections of horse apoferritin (HAF) for up to 56 days. At varying intervals, renal tissue was examined by light, immunofluorescence, and electron microscopy. Swiss mice developed proliferative glomerulonephritis after 7 to 14 days of HAF, and 45 per cent progressed to severe crescentic glomerulonephritis after from 21 to 56 days of HAF. In Swiss mice, glomerular immune deposits evolved from predominantly IgM mesangial deposits at 7 days to mesangial IgG at 14 days to capillary wall IgG after 21 or more days of HAF injections. BALB/c mice given identical HAF doses never developed severe crescentic glomerulonephritis but rather an extensive global necrotizing glomerulonephritis most prevalent after from 9 to 18 days of HAF. The distinct evolution of glomerular immune deposits observed in Swiss mice was less clear-cut in BALB/c mice, with greater persistence of mesangial deposits and IgM over time. Only 11 per cent of C3H mice (confined to two substrains) developed glomerular lesions by light microscopy after 2 to 3 weeks of HAF administration. No C3H/HeN mice developed glomerulonephritis even after up to 47 days of HAF injection. From 7 days on, 45 per cent of HAF-injected C3H mice had low level IgM mesangial immune deposits but did not manifest the evolution from mesangial to capillary deposition observed in BALB/c and Swiss albino mice. F1 hybrid and congenic mice carrying BALB/c H-2 genetic information developed glomerular lesions similar to those produced in BALB/c mice. These data (1) indicate an interrelated morphologic and immunohistologic evolution of heterologous protein induced glomerular lesions in mice, (2) demonstrate morphologic and immunohistologic differences in glomerular lesions development between genetically disparate mouse strains given identical antigen exposures, and (3) support the genetic control of heterologous protein-induced glomerulonephritis and suggest a role for the major histocompatibility region in this genetic regulation.     

Glomerulonephritis induced by murine chronic graft-versus-host reaction.

Severe glomerulonephritis was induced successfully in (B10 x DBA/2)F1 (BDF1) mice by injection of parental DBA/2 lymphoid cells. The mice manifested typical nephrotic syndrome dying around 10 weeks post injection. Electron microscopical examination demonstrated electron dense deposits first in the mesangial matrix, then in the subepithelium compatible with immune complex glomerulonephritis. Subendothelial deposits were not observed. Immunofluorescent study revealed IgG deposition in the capillary wall and IgM in the mesangium early in the process. As the lesion progressed, both IgG and IgM were present in the mesangial area and along the capillary wall. Some glomeruli showed segmental mesangiolysis, suggesting that altered mesangial cells have a role in the development of glomerular change, which together with rise in serum anti-DNA antibody titer suggest that autoantibodies promote the glomerular lesions in this model system.     

Glomerulonephritis Induced by Murine Chronic Graft-versus-Host Reaction

Severe glomerulonephritis was induced successfully in (B1OxDBA/2)F₁ (BDF₁) mice by injection of parental DBA/2 lymphoid cells. The mice manifested typical ne-phrotic syndrome dying around 10 weeks post injection. Electron microscopical examination demonstrated electron dense deposits first in the mesangial matrix, then in the subepithelium compatible with immune complex glomerulonephritis. Subendothelial deposits were not ob served. lmmunofluorescent study revealed IgG deposition in the capillary wall and IgM in the mesangium early in the process. As the lesion progressed, both IgG and IgM were present in the mesangial area and along the capillary wall. Some glomeruli showed segmental mesangiolysis, suggest ing that altered mesangial cells have a role in the develop ment of glomerular change, which together with rise in serum anti-DNA antibody titer suggest that autoantibodies promote the glomerular lesions in this model system. Acta Pathol Jpn 42 : 325–332, 1992.     

Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.

Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions.     

Immune complex glomerulonephritis mediated by thyroid antigens.

Hypothyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. A renal biopsy specimen showed increased mesangial cells and matrix with focal glomerular basement membrane thickening. Three years later, a pronounced increase in proteinuria was detected. Elevated levels of antibody to thyroid microsomal antigen and thyroglobulin were found in the serum. A renal biopsy specimen showed a pronounced increase in mesangial cells and matrix with generalized glomerular basement membrane thickening. Electron microscopic studies demonstrated granular deposits in the capillary walls and mesangium. Immunofluorescent studies revealed granular deposits of IgG, IgM, and C3, primarily on the glomerular basement membrane. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were detected with antibody specific for thyroglobulin and thyroid microsomal antigen. These observations suggest development of immune complex glomerulonephritis mediated by thyroid antigens.     

Experimental proliferative glomerulonephritis in the cat.

A model of chronic serum sickness was used to induce immune-complex glomerulonephritis in seven experimental cats, by daily intravenous inoculation of an increasing dose (5 to 35 mg) of human serum albumin (HSA). At week four, two of the seven animals developed anterior uveitis. At week 23, two different animals developed the subcutaneous oedema characteristic of the nephrotic syndrome (NS), whilst the other five cats appeared clinically normal. The kidneys were examined at necropsy by light microscopy and by transmission electron microscopy. The glomeruli of four animals (three with both proteinuria and uraemia, and one with proteinuria only) showed morphological changes under light microscopy. The abnormalities suggested that a diffuse mesangial proliferative glomerulonephritis (GN) had been induced in three cats and diffuse membranoproliferative GN induced in another. Ultrastructural studies revealed electron-dense deposits (immune-complexes) in six of the seven cats. Two cats without glomerular abnormalities by light microscopy had mesangial deposits and three cats with mesangial proliferative GN had deposits at mesangial, subendothelial and/or subepithelial sites. The single cat with membranoproliferative GN had deposits at mesangial, subendothelial, subepithelial and intramembranous sites. Immunohistological examination (peroxidase-antiperoxidase technique) showed that HSA and immunoglobulin (IgG and IgM) were deposited in the glomeruli of these cats. Deposits were the most dense in cats with more severe renal lesions. Deposits of IgM were most abundant. An extensive cellular infiltrate, comprising macrophages, neutrophils and plasma cells, was observed only in the four animals which showed abnormalities in glomerular ultrastructure. The disease induced in these cats thus appears to differ from the membranous nephropathy previously described in the cat and bears a close resemblance to immune complex (IC) disease in man. In view of the relatively few specific animal models of IC-mediated proliferative GN, this model has potential for application to the study of human IC disease.     

Naturally Occurring Immune-Complex Glomerulonephritis in Monkeys (Macaca irus): I. Light, Immunofluorescence and Electron Microscopic Studies

Light, immunofluorescence and electron microscopic studies were carried out on renal biopsies from 32 randomly selected adult monkeys (Macaca irus). Histopathology was limited to glomeruli and consisted of mild to moderate segmental increases in mesangial cells, mesangial matrix, and/or glomerular basement membrane (GBM) thickness in 41% of the animals. Granular deposits of IgM were present in the mesangial region and along the GBM in 72% of the monkeys, whereas IgG, C1q, C4 and C3 were detected in approximately 30%. Electrondense deposits were seen predominantly in epithelial foot processes adjacent to the GBM and, to a lesser extent, in the mesangium. Those monkeys with the heaviest IgM deposition were found to have decreased serum levels of C3, IgM and IgA. Follow-up biopsies over a period of 3 to 11 months revealed that the disease process was persistent yet nonprogressive. No correlation with age or sex was noted. All animals examined were clinically healthy and had normal renal function. This is the first documented occurrence of spontaneous immune-complex glomerulonephritis in a large monkey population. It appears to be a persistent disease which does not progress to renal insufficiency and which may serve as an investigative model for mild nonprogressive forms of human glomerulonephritis.     

Clinicopathologic features of young and old sphha/sphha mice. Mutants with congenital hemolytic anemia.

A colony of mice with congenital hemolytic anemia, sphha/sphha, were evaluated over a 3-year period. Prominent findings included decreased survivability, reticulocytosis, increased peripheral blood leukocytes, extramedullary hematopoiesis in liver and spleen, lymphoid hyperplasia and membranoproliferative glomerulonephritis. Older (12 to 21 months) anemic animals had elevated serum levels of IgG1 and IgA. There was deposition of C3, IgG, IgM, and IgA in renal glomeruli of both control and anemic mice, but deposition of IgM and IgA was more prominent and widely distributed in anemic animals and correlated with mesangial expansion and the presence of electron dense deposits in the mesangium and in glomerular capillary walls. Prominent renal tubular hemosiderosis was noted in young and old anemic mice. The relation between the hemolytic anemia and glomerular disease is unclear but these mice may be an animal model useful for exploration of changes attendant with chronic hemolysis and evaluation of renal disease that accompanies hemolytic anemia.     

Progressive cytomegalovirus glomerulonephritis - An experimental model.

Although acute infection with murine cytomegalovirus (MCMV) resulted in a transient focal glomerulonephritis characterized by mesangial inclusions, infection of HA/ICR mice given antilymphocyte globulin (ALG) led to progressive glomerulonephritis and renal failure. ALG alone without virus failed to produce progressive renal disease. Mice given both MCMV and ALG developed severe proteinuria and azotemia with glomerular crescents by 30 days. By immunofluorescence, viral antigen was limited to mesangial zones and glomerular axial poles. Granular deposits of rabbit IgG from ALG, mouse IgG, and C3 along the peripheral glomerular capillary walls were first observed 12 days after infection. By electron microscopy, virus was found only in glomerular mesangial cells that resembled macrophages. Intramembranous and subepithelial deposits in peripheral capillary walls were associated with accumulations of polymorphonuclear leukocytes dissecting into glomerular basement membranes. These observations best fit a multiphasic mechanism of glomerular injury initiated by persistent virus in the mesangium, followed by deposits of rabbit IgG from ALG, mouse IgG, and C in the peripheral capillary walls, resulting in an amplified immune-complex-mediated injury. Because other viruses localize within the glomerular mesangium, viruses should be considered potential causes of mesangial injury and progressive glomerulonephritis.     

The role of mesangial complement in the hematuria of experimental IgA nephropathy

We sought to determine if codeposits of IgG and IgM and glomerular complement, observed in most cases of human IgA nephropathy, might be important for inducing hematuria. All combinations of three binary variables, the protein immunogen, the duration of oral immunization, and the protein used for intravenous challenge, were accommodated by eight groups of BALB/c mice in an active model of IgA nephropathy. Mice drank 0.1% solutions of either of two proteins for either 6 or 14 weeks, and then were challenged intravenously with either the same protein or the alternate protein. After 6 weeks, all mice had significant increases of serum IgA, IgG, and IgM antibody to the oral immunogen. At 14 weeks, IgG and IgM antibodies were reduced, presumably due to the onset of oral tolerance, but IgA titers persisted. Nearly all mice had mesangial deposits of IgA and oral immunogen. However, only mice immunized for 6 weeks and challenged with the same protein had significant IgG and IgM deposits (100%), C3 deposits (76%), and significant microhematuria. To distinguish between the role of IgG/IgM codeposits and C3 in the pathogenesis of the hematuria, we induced passive IgA nephropathy with immune complexes of monoclonal IgA anti-dinitrophenyl antibody, dinitrophenyl-bovine albumin as antigen, and one of two monoclonal IgG antibodies specific for dinitrophenyl; one of the IgGs fixes complement, the other does not. Despite comparable mesangial deposits of IgA, IgG, and antigen, only mice given immune complexes containing the complement-fixing IgG had glomerular C3 and hematuria. Furthermore, when mice depleted of serum complement via cobra venom factor were given immune complexes containing the complement-fixing IgG, no glomerular complement was observed and no hematuria ensued. We conclude that IgG/IgM codeposits in murine IgA nephropathy do not directly cause hematuria but do induce the deposition of complement, which is in turn required for glomerular injury.     

Presence of immunoglobulin M antibodies around the glomerular capillaries and in the mesangium of normal and passive Heymann nephritis rats

Summary Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats.     

Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis

Renal glomerular disease characterized by the deposition of immunoglobulin light chains or monoclonal immunoglobulins was demonstrated by immunofluorescence microscopy in 11 patients. The most common histopathologic findings were those of mesangiocapillary glomerulonephritis, but considerable variability was observed. Lesions resembling diabetic glomerulosclerosis and amyloidosis were seen in some patients. Immunofluorescence findings in seven patients showed concomitant, equally intense staining for kappa light chain and immunoglobulin heavy chain (IgG or IgA), indicative of monoclonal immunoglobulin deposition. Specimens in the remaining cases stained predominantly for kappa light chain alone. In six cases the histologic and ultrastructural pattern was similar to that of type I mesangiocapillary glomerulonephritis. In three cases linear deposits were present, predominantly in subendothelial and inner glomerular basement membranes and, to a lesser degree, in mesangial locations, as in type II mesangiocapillary glomerulonephritis. In one of the latter cases dense deposits were intermixed with aggregates of amorphous fibrillar material indistinguishable from amyloid. In two cases involving IgA kappa chain deposition the histologic and ultrastructural appearance was that of mesangial glomerulonephritis. Considerable heterogeneity was found in the clinical features of the patient population. Specific clinical or serologic parameters for this disease could not be identified. Only one patient had an associated lymphoplasmacytic disorder. After follow-up periods ranging from six months to 17 years, all of the patients were alive, including four who had progressed to end-stage renal disease and required dialysis. Two of the latter patients underwent successful renal transplantation; one had been alive for five years and the other for three months without evidence of recurrence of the renal disease at the last follow-up examination.     

Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit

Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group.     

Heterogeneous IgA glomerulonephropathy in liver cirrhosis

Kidney and liver sections were obtained from 75 consecutive autopsy cases with liver cirrhosis discovered at post-mortem. Mesangial IgA as the predominant immunoglobulin was found in 36% (27) cases, with accompanying IgM in 10, and IgG in three subjects. IgA deposits occurred more frequently in micronodular cirrhosis than in macronodular and mixed types. There was no direct correlation with alcoholism or HBs antigen-orcein positivity in livers. The IgA antigen-antibody complexes formed against infectious and/or dietary antigens may bypass the liver phagocytic system via collateral shunts and cause the mesangial IgA deposits. IgA-bearing plasma cells in the liver (80%) may also contribute to the deposits. In cases of liver cirrhosis, there was a variable glomerular morphology including normal appearance by light microscopy (32%), minor changes (38.7%), diffuse mesangial sclerosis (12%), diffuse mesangial cell proliferation, and infrequently membranous and diffuse proliferative glomerulonephritis with a 'lobular pattern'. Five (6.7%) cases showed focal and segmental mesangiolysis with glomerular aneurysms, probably caused by toxic and/or infective agents bypassing the liver reticuloendothelial phagocytic system and acting on the mesangium to cause rupture of anchor points and formation of capillary aneurysms. The cirrhotic glomerulonephropathy was usually clinically latent, but two biopsy cases with mesangiocapillary glomerulonephritis had developed a nephrotic syndrome.     

Pathological implications of linear immunoglobulin G staining on the glomerular capillary walls in a case of infection‐related glomerulonephritis

We report a 32‐year‐old man with nephrotic syndrome and preceding symptom of infection. He had renal insufficiency, hypocomplementemia, and elevated titer of anti‐streptolysin O. Renal biopsy showed mesangial hypercellularity and focal segmental endocapillary hypercellularity with double contour of the glomerular basement membrane (GBM). Immunofluorescence study showed granular C3 staining on the mesangial areas and glomerular capillary walls (GCWs) and linear immunoglobulin G (IgG) staining on GCWs. Electron microscopy revealed sporadic subepithelial humps, discontinuous small and thin deposits in the endothelial side of the GBM and mesangial deposits. He was diagnosed with infection‐related glomerulonephritis (IRGN) with the striking finding of linear IgG staining, which is unusual in IRGN. The patient did not have diabetes mellitus or anti‐GBM disease. The patient's serum seemed not to contain IgG, which can bind to GCW. He showed normalization of complement within two months after relief from infection symptoms and a trend toward improvement in proteinuria, hematuria and renal function over 14 months. We discuss the possible mechanisms of linear IgG staining in our case based on clinical and experimental studies on IRGN with cationic bacterial protein as antigen.