A rare case of PLA2R- and THSD7A-positive idiopathic membranous nephropathy / Positividade tecidual dupla para PLA2R e THSD7A em nefropatia membranosa idiopática: raro relato de caso

ABSTRACT Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.

RESUMO A Nefropatia Membranosa Idiopática (NMi) é uma frequente causa de síndrome nefrótica em adultos e sua etiologia pode ser estratificada em primária/idiopática ou secundária. O conhecimento da fisiopatologia da NMi sugeriu a presença de autoanticorpos (PLA2R e a THSD7A) direcionados contra antígenos existentes nos podócitos. A detecção de anticorpos contra um domínio favorece NMi. A presença de autoanticorpos contra um desses domínios autoexcluiria a possibilidade de autoanticorpos contra o outro domínio; no entanto, recentemente foram descritos casos que apresentaram dupla positividade para PLA2R e THSD7A, comprovando que, por mecanismos fisiopatológicos ainda não conhecidos, raramente pode existir produção concomitante de anticorpos contra os dois alvos. O presente estudo tem por objetivo relatar o caso de um paciente de 46 anos de idade, do sexo masculino, que apresentou quadro de proteinúria nefrótica, hematúria, hipoalbuminemia e hipercolesterolemia submetido a biópsia e exame histopatológico (ML, IF, IHQ e ME), confirmando um caso raro de NMi com positividade dupla para os anticorpos anti-PLA2R e anti-THSD7A e associação à nefropatia por IgA, mostrando nossa experiência com a utilização de subclasses de IgG, PLA2R e THSD7A na rotina laboratorial para a investigação da GNM e enfatizando a importância de uma abordagem ampla para adequada elucidação e conhecimento dos mecanismos fisiopatológicos na NMi.

Lack of significant association between rosette formation and parasitized erythrocyte adherence to purified CD36.

The ability of Plasmodium falciparum infected erythrocytes from 162 Thai patients with uncomplicated malaria, 82 patients with severe malaria and 19 patients with cerebral malaria to form rosettes in vitro was studied. Of 263 isolates, 62 were evaluated for their adherence to different target molecules. We found that wide variation occurred in isolates from all groups in the level of rosette formation and adherence to CD36, intracellular adhesion molecule-1, thrombospondin and chondroitin sulfate A. No statistically significant correlation between the magnitude of rosette formation and disease severity was found (p > 0.05). In addition, our results from the use of purified CD36 as an adherence receptor showed no association between the degree rosetting and level of cytoadherence (p > 0.05, r = -0.04). Our data provide evidence that rosette formation and cytoadherence involve different molecular mechanisms and both phenomena can occur in all manifestations of the disease.