Chronic granulomatous disease presenting as fulminant Aspergillus pneumonitis: a lethal combination?

OBJECTIVE: Case reports of two patients with unusually late initial presentation of chronic granulomatous disease with fulminant Aspergillus pneumonia. DATA SOURCES AND EXTRACTION: Medical notes; retrospective study. STUDY SELECTION: Identical pattern of clinical presentation in two patients referred for support with extracorporeal membrane oxygenation (ECMO). Our Institutional Review Board waived the need for consent. DATA SYNTHESIS: Two school-aged boys presented with features of, and were initially treated, for community-acquired pneumonia. However, the disease course was rapidly progressive to fulminant respiratory failure and because both failed conventional intensive care management, they were referred to ECMO support. Although both died of evolving multiorgan failure, ECMO support allowed open lung biopsy leading to diagnosis of invasive Aspergillus pneumonia and chronic granulomatous disease. CONCLUSIONS: Failure of adequate therapy for acute community-acquired pneumonia and rapid progression to respiratory failure should lead to the possibility of fungal etiology. Congenital immunodeficiency may present for the first time late in life, so acute invasive pulmonary aspergillosis in the absence of known risk factors should lead to consideration of chronic granulomatous disease regardless of patient age.

T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice.

AIM: To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine T cell specificity against the arthritogenic CII(259-273) epitope of type II collagen either unmodified or post-translationally glycosylated at Lys(264). METHODS: Arthritis was induced by immunisation with human type II collagen in complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays, using T cell hybridomas specific for the glycosylated and non-glycosylated CII(259-273) epitope. RESULTS: The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non-glycosylated epitope than to the glycosylated CII(259-273). Most of the T cell hybridomas generated from CII-immunised mice recognised the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells. CONCLUSION: This study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC-II, which could contribute to the pathogenicity of autoimmune arthritis.