Granular Deposits Of IgG Research Articles

Murine Susceptibility to Mercury: II. Autoantibody Profiles and Renal Immune Deposits in Hybrid, Backcross, and H-2d Congenic Mice

Inorganic mercury causes systemic autoimmunity and/or immune-complex deposits in strains of mice carrying certain H-2 haplotypes, for example H-28 and H-2 d. This study aimed at describing the genetic mechanisms regulating these reactions. Inbred SJL, C57BL/6J (B6), C57BL/10J (B10), and DBA mice, F1(SJL × DBA), F1(SJL × B6), and F2(SJL × B6) hybrids, and mice derived from a backcross of SJL or B6 mice to F1(SJL × B6) hybrids were given subcutaneous injections of either 1.6 mg HgCl 2/kg body wt or 0.1 ml NaCl every third day for 6 weeks. SJL mice developed a high titer of serum antinucleolar antibodies (ANoA) of the IgG class targeting the nucleolar protein fibrillarin and a significantly increased titer of IgG and C3 colocalized as granular deposits in the renal mesangium and vessel walls. The B6 and DBA strains lacked ANoA and showed no increase in titers of immune deposits. Nine percent of mercury-treated F1(SJL × DBA) hybrids developed IgG-ANoA which were of a low titer, and only occasional hybrids showed an increased titer of granular mesangial IgG deposits. Mercury treatment induced ANoA of low titer in 41% of F1(SJL × B6) hybrids, and 24% had increased granular mesangial immune deposits. Four of 61 mercury-treated BC[SJL × F1(SJL × B6)] mice showed ANoA which were of a high titer and targeted the nucleolar protein fibrillarin. ANoA were not found in 55 mercury-treated F2(SJL × B6) hybrids or in 56 mercury-treated mice derived from a backcross of B6 mice to F1(SJL × B6) hybrids. Increased mesangial immune deposits were regularly accompanied by vessel wall deposits in F1- and F2(SJL × B6) hybrids, but only 53% of BC(SJL × F1[SJL × B6]) mice with increased mesangial deposits had vessel wall deposits. Vessel wall immune deposits were only present in mice with increased mesangial deposits. A majority of mice which developed significantly increased titers of mesangial IC deposits showed no ANoA. In conclusion, the susceptibility in SJL mice to develop ANoA during mercury treatment, which has been shown to reside in the H-2A locus, was codominantly inherited in a cross with mice carrying the H-2 b and H2 d haplotypes. NonH-2 genes dampened ANoA expression to a degree which varied between the strains. Since renal vessel and mesangial IC deposits developed in backcross mice lacking serum ANoA, these deposits must contain IC not related to fibrillarin-antifibrillarin. In BALB/c mice, lacking antinuclear antibodies, the development of renal mesangial and vessel wall immune complex deposits during mercury treatment was found to be linked to one or more H-2 loci to the right of the A region and codominantly inherited in a cross to B6 mice. The extent of these immune complex deposits was also strongly modified by non-H-2-genes with the degree of dampening varying between different mouse strains.

Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat

Subcutaneous injections of mercuric chloride induce an autoimmune glomerulonephritis with both granular and linear IgG deposits along the glomerular capillary wall and proteinuria. This disease is due to a T cell dependent polyclonal B cell activation responsible for production of antibodies against self (glomerular basement membrane, immunoglobulins, DNA, myeloperoxydase) and non self (sheep red blood cells, trinitrophenol (TNP)) components. Increase in serum IgE concentration is the hallmark of this disease. To determine if mercury vapours have pathogenic effects is an important problem of public health. The aim of this study was, first to compare the effects of mercury vapour exposure to those of mercury injections and, second, to compare the effects of high doses to those of low doses of mercury. Two exposure levels were studied corresponding to a mercury absorption of 13.1 μmol/week per kg body wt. and 1.7 μmol/week per kg body wt. during a 5-week period. It will be shown that, whereas the mercury concentration in the kidneys was similar in injected —and vapour exposed — rats, the mercury concentration in blood at the end of the exposure was about twice as high in the injected animals. Bllod concentration of mercury was related to dose level but kidney content of mercury was similar in all groups, in spite of a dose difference by a factor seven between low and high exposure.Mercury vapour and HgCl 2 injections both trigger autoimmunity to the same extent and, in both cases the extent of autoimmune manifestations was dose-dependent.

Brunsting-Perry cicatricial bullous pemphigoid: A clinical variant of localized acquired epidermolysis bullosa?

An 84-year-old man who had the typical clinical features of Brunsting-Perry cicatricial pemphigoid is described. Direct immunofluorescence microscopic examination of salt-split skin revealed linear deposits of IgG and C3 on the floor of the artificial bullae. Direct immunoelectron microscopic examination of peribullous skin showed dermal cleavage level below the lamina densa and granular deposits of IgG and C3 attached to and below the lamina densa in a pattern identical to epidermolysis bullosa acquisita. These findings suggest that Brunsting-Perry cicatricial pemphigoid may represent a clinical variant of epidermolysis bullosa acquisita.

Transfer of Experimental Autoimmune Thyroiditis by in Situ Perfusion of Thyroids with Immune Sera

The role of autoantibodies in the pathogenesis of autoimmune thyroiditis (AT) still remains poorly understood. Serum transfer experiments in experimental AT (EAT) and spontaneous AT (SAT) animal models frequently did not succeed or only resulted in minor thyroid lesions. The inconsistent results may have arisen because of technical problems inherent in serum transfer, the major of which is to obtain high enough concentrations of autoantibodies over long enough periods at the potential site of tissue injury. An attempt was made to circumvent this hurdle by repeated in situ perfusions of the rabbit thyroid via the superior thyroid artery. In situ perfusion of rabbit thyroids with high-titered homologous sera reactive with saline thyroid extract indeed led to thyroiditis characterized by granular deposits of rabbit IgG and C3 in the thyroid follicular basal laminae, cellular infiltrates consisting of mononuclear cells and granulocytes, destruction of the thyroid follicular architecture, and focal fibrosis. Perfusion with control sera lacking thyroid-reactive antibodies did not lead to thyroid lesions. These results demonstrate that humoral antibodies can induce severe AT comparable to actively induced thyroiditis.

Penicillamine-lnduced Rapidly Progressive Glomerulonephritis in a Patient with Rheumatoid Arthritis

A 67-year-old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg/day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D-penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D-penicillamine and vigorous treatment measures could allow for a good prognosis as in this case.

Murine susceptibility to mercury: I. Autoantibody profiles and systemic immune deposits in inbred, congenic, and intra-H-2 recombinant strains

Inbred, congenic, and intra-H-2-recombinant mouse strains were given subcutaneous injections of either 1.6 mg HgCl 2/kg body wt or 0.1 ml NaCl thrice weekly for 5–6 weeks. Mercury-treated mice from strains carrying the H-2 s haplotype developed antinucleolar antibodies (ANoA), which targeted the 34-kDa nucleolar protein fibrillarin, and in some instances also nucleolar proteins of 60–70 and 10–15 kDa, the latter corresponding to histones. Strains with H-2 b and H-2 d haplotypes were resistant to induction of ANoA. The susceptibility to development of ANoA/antifibrillarin antibodies (AFA) was mapped to the H-2A-region using intra-H-2-recombinant strains. We were not able to confirm earlier reports that expression of H-2E genes dampens the development of ANoA. Mercury treatment caused a substantial increase in the titer of antichromatin (ACA) and/or antihistone (AHA) antibodies in a fraction of SJL/J, A.SW, A.TH, B10.S, and B10.HTT mice (H-2 s), and in A/J (H-2 k) mice, whereas mice from the C57BL/6J and C57BL/10J (H-2 b), and the DBA and BALB/c (H-2 d) strains were low or nonresponders. The development of AHA and ACA could not be linked to the H-2 complex. A significant, substantial increase of granular mesangial and systemic vessel wall IgG deposits occurred in mice with serum ANoA/AFA. However, the B10.S(9R) and B10.HTT strains, which express the H-2E genes, developed only an intermediately increased titer of mesangial IgG deposits. Systemic vessel wall IgG deposits occurred in only 60–80% of the B10.S(9R)mice and in none of the B10.HTT mice. This contrasted with the high titer of mesangial IgG deposits and uniform development of systemic vessel wall IgG deposits observed in B10.S mice not expressing H-2E. Mice with mesangial IgG deposits showed a mild glomerulonephritis. There was no systemic vasculitis. The susceptibility to development of ANoA, AHA, ACA, and systemic, granular IgG deposits in the B10.S strain was influenced by the sex, since males showed less uniform development of these immunopathologic features than females.

Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease

Female SJL N mice were given either 5.0, 2.5, 1.25, or 0.625 mg mercuric chloride per liter drinking water (ppm HgCl 2). Serum antinucleolar antibodies (ANuA) of the IgG class were scen in mice given at least 1.25 ppm HgCl 2 for 10 weeks, a dose which corresponded to a mean renal mercury concentration, as measured with atomic absorption spectrophotometry, of 2.4 ± 0.43 μg Hg/g wet weight (ppm Hg; means ± 1 SD). At a dose of 5.0 ppm HgCl 2 all mice showed IgG ANuA with a mean titer of 1:846 and a mean renal mercury concentration of 14.8 ± 3.9 ppm. Significantly increased titers of granular IgG deposits, corresponding to immune-complex (IC) deposits, developed in the renal mesangium of mice given 5.0 ppm HgCl 2. Mice with heavy mesangial IgG deposits showed a mild glomerular endocapillary cell proliferation and widening of the mesangium. Renal vessel wall IgG deposits were found only in mice given 5.0 ppm HgCl 2, whereas such deposits were seen in splenic and cardiac arteries of mice receiving 1.25 ppm or more of HgCl 2. The renal and splenic mercury concentration was significantly increased in all groups of mercuric chloride-exposed mice and correlated with the dose. We conclude that 10 weeks peroral treatment with mercuric chloride in drinking water is able to elicit autoimmunity and IC disease in genetically homogeneous, mercury-sensitive mice at a body burden similar to that reported in some occupationally exposed humans.

Incidence of Alopecia Areata in Lupus Erythematosus

A small percentage of patients with alopecia areata have connective diseases such as systemic lupus erythematosus, discoid lupus erythematosus, rheumatoid arthritis, and scleroderma. Lupus erythematosus is associated with a number of different types of alopecia, but the incidence of alopecia areata in lupus erythematosus has not been examined. Of our cohort of 39 patients with lupus erythematosus, alopecia areata developed in 10% (four patients), in contrast to 0.42% of general dermatologic patients. Biopsy specimens of alopecia areata lesions in each of our patients showed continuous granular deposition of IgG at the dermoepidermal junction, a finding usually found in only a minority of alopecia areata cases. Intralesional injections of corticosteroids were effective treatment. The incidence of alopecia areata in patients with lupus erythematosus is increased. Recognition of this form of alopecia allows for specific therapy with intralesional corticosteroids.

Acute glomerulonephritis in association with a cutaneous infection due to Staphylococcus aureus

Immune complex glomerulonephritis developed in a 65-year-old patient with thoracic surgical wound infection by Staphylococcus aureus without bacteremia. Despite adequate antimicrobial therapy renal function remained impaired and a second renal biopsy demonstrated a diffuse extracapillary proliferative glomerulonephritis and granular deposition of IgG and C3 components within the glomerulus. Our experience supports the contention that some cases of glomerulonephritis may be caused by staphylococcal skin infections.

Composition of immune deposits present in glomeruli of NZB/W F 1 mice

This paper describes the results of experiments designed to investigate the composition of immune complexes present, in the form of immune deposits, in glomeruli of NZB/NZW F1 mice. Granular deposits of mouse IgG were present along the glomerular capillary walls of 6- to 12-month-old mice. Disappearance of mouse IgG from glomerular deposits, indicating a dissociation of immune complexes, was observed following incubation of kidney sections with an excess of mouse IgG, mouse Fc fragments, rat IgG, and rat Fc fragments, but not with human and rabbit Cohn fraction-II (FII), DNA, nucleohistone, and PBS. Antinuclear antibody activity in mouse sera or in glomerular eluates was removed by absorption with mouse IgG or mouse Fc fragments, rat IgG or rat Fc fragments, DNA, and nucleo-histone, but not by absorption with human or rabbit FII. These results suggest that the IgG antinuclear antibodies present in the sera and in glomerular deposits possess rheumatoid factor (RF) activity. In other experiments, kidney sections were incubated with various concentrations of pepsin, which digests the Fc portion of the IgG. After digestion, the sections were washed and stained for mouse IgG, IgG F(ab')2, and IgG Fc. At concentration of 10 micrograms/ml, pepsin completely removed IgG and IgG Fc, whereas faint IgG F(ab')2 deposits persisted in glomerular deposits. At the concentration of 1 microgram/ml, deposits of mouse IgG, F(ab')2, and Fc persisted, while F(ab')2 was observed bound to nuclei of glomerular cells. At the pepsin concentration of 0.1 microgram/ml or 0.01 microgram/ml, IgG F(ab')2 was bound to the nuclei of glomerular and tubular cells, indicating that the digestion of the Fc portion of IgG had released F(ab')2 with nuclear reactivity from glomerular deposits. The solubilization of mouse IgG from glomerular immune deposits with mouse IgG and the demonstration that pepsin digestion releases mouse F(ab')2 with nuclear reactivity are consistent with the interpretation that the immune deposits present in glomeruli of NZB/NZW F1 mice contain complexes formed by antinuclear IgG and IgG RF. These two antibodies probably cross-react and form multilayer aggregates which contribute to the formation of immune deposits.

Acquired Epidermolysis Bullosa With the Clinical Feature of Brunsting-Perry Cicatricial Bullous Pemphigoid

A 56-year-old woman with the typical clinical feature of cicatricial bullous pemphigoid of the Brunsting-Perry type was studied. Histologic examination of a lesion skin biopsy specimen demonstrated a subepidermal blister. Direct immunofluorescence microscopy revealed linear deposits of IgG, IgM, and C3 located on both the roof and the floor of the blister. Immunofluorescence antigen mapping using cryostat sections of a spontaneous blister and antisera against defined basement membrane components localized the bullous pemphigoid antigen and type IV collagen in the roof of the blister. This dermal type of blister formation was confirmed by electron microscopy, which showed the cleavage level below the lamina densa. In direct immunoelectron microscopy, granular deposits of C3 and IgG were found attached to and just beneath the lamina densa in a pattern identical to the distribution of anchoring fibrils. These findings are diagnostic of acquired epidermolysis bullosa, a blistering disease that has much more clinical heterogeneity than previously suggested.

Study on the swine glomerulopathy resembling human IgA nephropathy

Naturally occurring swine glomerulopathy was investigated and its glomerular tissue injury was compared with that of human IgA nephropathy. Mild proteinuria (30%) and microhematuria (17%) was found in 30 six-month-old swine. Serum creatinine level was 1.8 +/- 0.4 (mean +/- SD) mg/dl. Light microscopy (LM) disclosed diffuse or focal glomerulopathy with mesangial enlargement and hemispherical deposits in six-month-old swine. Electron microscopy revealed dense deposits in the mesangial, para-mesangial and sub-endothelium areas. On immunofluorescence+ (IF) staining findings, granular deposits of IgA (97%), IgG (97%), IgM (80%), C3 (100%), and mycoplasma hyorhinis (MH) antigen (90%) were found in the mesangial areas and along the capillary walls. One three-month-old pig and one five-year-old Goettingen mini pig were also found to have granular deposits of immunoglobulin and MH antigen in the glomerulus. In contrast, no glomerular lesion was found in all 4 new-born pigs and 4 fetal pigs by LM and IF study. In six-month-old swine anti-nuclear factor and anti-DNA antibody were negative, and no pathological lesion was found in the liver by LM. And IgA and MH antigen containing circling immune complexes were positive in sera by Raji cell assay, and moreover IgA and MH antigen was found co-depositing by the double stain techniques. These findings suggest that swine glomerulopathy is similar in appearance to human IgA nephropathy and MH antigen may contribute to the development of this nephropathy.

Lupus Nephritis in Autoimmune‐prone NZBxNZW F1 Mice and Mechanisms of Transition of the Glomerular Lesions

The pattern of renal glomerular lesions in systemic lupus erythematosus (SLE)-prone NZB x NZW (B/W) F1 mice shows an age-associated transition, as is often seen in human lupus nephritis during the clinical course of the disease. Observations revealed that the earliest lesions were confined to the mesangium associated mainly with IgM deposits, and to a lesser degree with IgG. In mice over 5 months of age, the lesions extended gradually to the capillary wall with fine granular subepithelial deposits of IgG, but not of IgM. The ultimate pattern of the glomerular lesion was one of diffuse proliferation with diffusely distributed deposits of both IgG and IgM in the mesangium and along the capillary wall. Even at this stage, subepithelial deposits were composed of IgG, but not of IgM. The pattern of glomerular deposits of endogenous retroviral envelope glycoprotein gp70, which is highly anionic, virtually coincided with that of IgG. Taking these findings collectively, it is suggested that the progression of glomerular lesions in B/W F1 mice depends largely on the age-associated appearance of retroviral gp70-IgG anti-gp70 immune complexes in the circulation and their deposition along peripheral subepithelial, and eventually subendothelial areas.

Renal Involvement in Canine Leishmaniasis

In a prospective survey in the Isle of Elba, 413 dogs affected by naturally acquired Leishmania infantum infection were identified out of a controlled population of 1,500 resident mongrel dogs. In all the 34 randomly selected dogs of different breed, age, and duration of disease, the presence of glomerular lesions which defined mainly two categories of glomerulonephritis (GN) was observed. The first group was characterized by mesangial-cell proliferation either with focal features (11 dogs), or with a diffuse pattern (10 dogs). The second group (12 dogs) showed the typical findings of segmental membrano-proliferative GN; amyloid deposits were seen in the glomerular tuft and interstitium in 1 dog. Immunohistochemical investigation revealed granular deposits of IgG, IgM, and C3 both in mesangial areas as well as on glomerular capillary walls. Granular immune deposits om the tubular basement membrane were also found in 31 out of 34 dogs examined. With ultrastructural investigation, subendothelial and mesangial electron-dense deposits were revealed. Age, sex, serum creatinine, BUN, duration of disease, anti-Leishmania antibody titers, and immune complexes did not discriminate between the types of observed GN, while proteinuria did. The study shows that the renal involvement is the natural sequela in dogs infected with L. infantum, and that the kidney lesions are characterized by immunologically mediated glomerular and tubular damage.

Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin

Membranous nephropathy was induced in four cats by repeated intravenous injections of 120 mg cationic bovine serum albumin ( bsa, pI 9·5). All four cats developed diffuse granular deposits of IgG and C3 along the glomerular capillary walls as early as five weeks which persisted until the end of the experiment at 17 weeks. Ultrastructural studies revealed many subepithelial electron dense deposits. Two cats developed severe proteinuria and the nephrotic syndrome characterised by hypoalbuminaemia and oedema. An additional four cats received repeated injections of unmodified native BSA (pI 4·5) and remained basically normal. This is the first report of membranous nephropathy and the nephrotic syndrome in an experimental animal model which, unlike other animal models, is subject to the spontaneously occurring disease.

Papular and Nodular Mucinosis as a Sign of Lupus erythematosus

We describe 3 cases of papular and nodular mucinosis (PNM), a clinically distinctive cutaneous mucinosis associated with lupus erythematosus (LE), which has received little attention in the dermatologic literature. Histopathology shows deposits of mucin in the dermis without microscopic features of LE, while immunofluorescent studies disclose linear or granular deposits of IgG, IgM and C3 at the dermoepidermal junction. In about 80% of the 14 cases described in the literature, PMN has been associated with systemic LE with prevalent joint and kidney involvement. The possible prognostic significance of this singular dermatosis is discussed.

Specificity and cross‐reactive idiotypes of anti‐glomerular basement membrane autoantibodies in HgCl2‐induced autoimmune glomerulonephritis

Mercury-induced autoimmune glomerulonephritis in the Brown-Norway (BN) rat is characterized by the successive appearance of linear and granular glomerular IgG deposits. Anti-laminin autoantibodies represent the major part of the anti-glomerular basement membrane (GBM) antibodies produced in this model. Fusions were performed in this model and four anti-GBM monoclonal antibodies (mAb) were obtained. Three of them were laminin specific. Using rabbit anti-idiotype antibodies, cross-reactive idiotypes (CRId) were characterized on anti-laminin antibodies. They were expressed on the three anti-laminin mAb, on kidney-eluted and circulating anti-laminin antibodies. CRId-bearing immunoglobulins were detected transiently in the circulation and paralleled the anti-laminin antibody activity. By immunofluorescence studies on kidney cryostat sections two different CRId were defined. One was localized close to the antigen-combining site since it was not revealed on kidney-bound antibodies, in contrast with the second CRId. This latter CRId was also found deposited in a typical linear pattern in the early phase of the disease and in a granular pattern in the late phase, demonstrating that these CRId are components of immune deposits. Taken together, these results suggest that in this model of T-dependent polyclonal B cell activation, restricted sets of V genes encode for at least a part of the anti-GBM autoantibodies.

Experimental membranous glomerulonephritis in rats induced with gp 700, a glomerular protein

To investigate the antigenicity of glomerular cell products for the induction of Heymann nephritis (HN), eight Lewis rats were immunized with an isolated glomerular protein (GLP) with only limited tubular cell contamination. Four out of four rats immunized with 240 micrograms GLP showed proteinuria at week 12. Their kidney specimens taken at week 16 showed contiguous granular deposits of IgG along the glomerular basement membrane by direct immunofluorescence and corresponding electron-dense deposits; the findings were identical to those in classical HN induced by the brush border protein. By immunoprecipitation, IgG eluted from isolated glomeruli of rats that received 240 micrograms GLP precipitated only a 700 kd glycoprotein (gp 700) in GLP, whereas 330, 440, and 700 kd glycoproteins were precipitated in the crude preparation (Fx1A), which is derived mainly from renal tubules. Two different monoclonal antibodies (anti-gp 330 and 14C1) against gp 330 precipitated the antigens in the same fashion as the glomerular eluate. These data reveal that gp 700, gp 440, and gp 330 share epitopes and that the gp 700 is demonstrable both in the glomerulus and in tubular brush border but that gp 440 and gp 330 are present only in the brush border. In addition, glomerular gp 700 was shown to induce Heymann-type glomerulonephritis just as gp 330 did.

Elevated Plasma Fibronectin Levels in Rats with Immune and Toxic Glomerular Diseases

We measured plasma fibronectin levels by a rocket immunoelectrophoresis in rats with chronic serum sickness induced by repeated injections of ovalbumin and in rats with epithelial nephropathy induced by a single injection of adriamycin. In the early phases of the immune model, rats presented granular deposits of IgG in the mesangial area with no or descrete proteinuria (less than 40 mg/24 h). Fibronectin levels in that group were significantly higher (450 +/- 90 micrograms/mL) than in normal rats of the same age (350 +/- 46; p less than 0.01). When animals presented IgG deposits in the capillary wall, an important nephrotic syndrome developed in most of them. Fibronectin levels then increased very significantly (863 +/- 153 micrograms/mL; p less than 0.0005). In the model of adriamycin nephropathy, fibronectin significantly increased (580 +/- 110 micrograms/mL; p less than 0.0005) from the first week, when proteinuria was in a range 40-60 mg/24 h. However, the levels were higher (860 +/- 175 micrograms/mL; p less than 0.0005) when a complete nephrotic syndrome developed. At this time, plasma fibronectin levels correlated directly in both models with the degree of proteinuria and inversely with the total serum protein concentration. Our results show that plasma fibronectin levels increased very early in animals with immune and toxic damage of the kidney. The highest elevated values found thereafter, when a full nephrotic syndrome was present, suggest an increased synthetic rate of that glycoprotein linked to that situation.

Renal Disease in a Patient with Hereditary Complete Deficiency of the Fourth Component of Complement

Hereditary complete deficiency of the fourth component of complement (C4) is an extremely rare disorder with 17 cases reported so far. Twelve of these patients suffered from a systemic-lupus-erythematosus-like illness. The patient we here describe presented with severe Henoch-Schönlein purpura (HSP) at the age of 17. Immunofluorescence of a kidney biopsy showed granular deposits of IgG, IgA, IgM, C3 and fibrinogen in the mesangium and segmentally along the basement membrane. Six years later, the patient developed hypertension and nephrotic syndrome. Renal function deteriorated rapidly. He was on hemodialysis for 12 months and then received a cadaveric kidney graft. After 2 years of uncomplicated course, microhematuria and proteinuria developed. Immunofluorescence of a transplant biopsy was virtually identical to the pattern in the patient's own kidneys. We thus conclude that the patient had recurrence of his primary disease in the graft. Three and a half years after transplantation hemodialysis had to be restarted. This unique case supports the current view that deficiency of classical pathway components predisposes to the development of immune complex diseases and that the complement system is activated via the alternate pathway in HSP. Furthermore, we assume that complete C4 deficiency was the major cause for the recurrence and unfavorable outcome of HSP in the graft.