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Membranoproliferative glomerulonephritis (MPGN) is a glomerular pattern of injury due to different disorders and pathogenic pathways, thus amenable to diverse treatments. A systematic approach allows, in most cases, identification of the underlying cause and a specific treatment.
Report the case of a patient with nephritic syndrome, autoimmune phenomena with numerous autoantibodies, and a histological pattern of MPGN in the context of acute HIV infection.
A 35 year-old woman presented with lymphadenopathies and a two-month history of constitutional symptoms (fever and arthralgias). On admission: BP 190/110 mmHg, pernio erythema, livedo reticularis on lower limbs, nontender lymphadenopathies, and grade 1 splenomegaly. Laboratory findings revealed reactive HIV (viral load 528000 copies/mL, CD4 count 623 cells/mm3), serum creatinine 1.7 mg/dL, creatinine clearance 72 mL/min., proteinuria 3.8 g/24 hrs, urine sediment with hematuria and leukocyturia and albumin 2.8 g/dL. SPEP showed elevated serum proteins with a polyclonal appearance consistent with a chronic inflammatory profile. UPEP: selective proteinuria. ESR 120 mm/h, C3 60 mg/dL, C4 5 mg/dL. Rheumatoid factor < 9 IU/mL, negative cryoglobulins, positive anti-GBM antibodies (61 U/mL), ANA 1/640, anti-DNA 612 U/mL, ANCA MPO 26 UA and PR3 44 UA. Negative antiphospholipid antibodies. Blood and urine cultures were negative and co-infections (hepatitis B and C and syphilis) were ruled out. Echo was negative for endocarditis. Lymph node biopsy showed reactive lymphadenitis associated with HIV. Immunosuppressive therapy was initiated empirically with methylprednisolone followed by prednisone 1 mg/kg and kidney biopsy was performed. Renal histopathology revealed focal proliferative GN, 20% interstitial fibrosis and tubular atrophy, and arteriolar/arterial hyalinosis. Immunofluorescence was only positive for C3. Electron microscopy showed subepithelial deposits (humps). Antiretroviral therapy was initiated, resulting in a significant clinical and laboratory improvement. Renal function improved, with a decrease in serum creatinine (0.76 mg/dL), normalization of albumin and a decrease in proteinuria/creatinuria ratio (0.19 g/g). Regarding autoantibodies, ANA and ANCA turned negative, and complement levels normalized at 28 weeks after starting ART.
We present a case of a patient who presented with acute glomerulonephritis in the context of acute HIV infection with a histological diagnosis of C3 glomerulonephritis. Alternative complement pathway studies are ongoing. We hypothesize that immune response to acute HIV infection likely triggered dysregulation of the alternative complement pathway, probably due to antibodies directed against complement regulator proteins. C4d could help, being negative in C3 glomerulopathy and positive in HIVICK. Probably if we measure the activity of soluble C5b-9 we would observe the activation of the alternative complement pathway with a decrease in activity with the initiation of ART.
The originality of this case is the presence of numerous autoantibodies. This has been previously reported in HIV acute infection. Autoimmune diseases may develop due to immune dysfunction with predominant B cell polyclonal stimulation and molecular mimicry is one of the postulated mechanisms as well as excessive induction of NETS. However, the association of autoantibodies in HIV-infected patients to clinical autoimmune disease is yet to be established. In our patient these autoantibodies were non pathogenic, at least for the moment, and turned out negative after ART initiation.
The positivity of anti-GBM antibodies is of particular interest because of the high specificity. A few case reports have documented positivity in infections such as COVID, HIV and hantavirus.
This case underscores diagnostic and therapeutic dilemmas, emphasizing the importance of a systematic approach of the different etiologies to establish an accurate pathogenic diagnosis and treatment.