Azathioprine is commonly used in Crohn’s disease. It has been administered to many pregnant women over many years without significant side effects. However, pancytopenia and severe combined immune deficiency-like disease have been reported in infants whose mothers received azathioprine throughout pregnancy. Moreover, myelotoxicity has been described in patients being treated with azathioprine and having a low or absent thiopurine S-methyl transferase [TPMT] activity. Here, we describe the case of a newborn girl found to be highly lymphopenic [< 300 CD3+ T cells] after a positive newborn screening for severe combined immuno deficiency. The clinical examination was normal. The mother was treated with azathioprine throughout her pregnancy, without any reduction of the dose. It was shown that the mother was heterozygous for the 3A [TPMT] activity mutation and that the baby was homozygous for the same mutation; 6-thioguanine nucleotides were high (744 pmol/8.108 red blood cells [RBC]) in the mother and detectable in the infant [177 pmol/8.108 RBC]. Although rare, this case illustrates the potential grave consequences of unsuspected TPMT homozygosity in a newborn of a mother receiving thiopurines during pregnancy. Because of the severity of the risk for the newborn, consideration should be given to performing maternal genetic testing and newborn routine blood count in cases of thiopurine treatment during pregnancy.
Background Dendritic cells (DC) and regulatory cells (Treg) play pivotal roles in controlling both normal and autoimmune adaptive immune responses. DC are the main antigen-presenting cells to T cells, and they also control Treg functions. In this study, we examined the frequency and phenotype of DC subsets, and the frequency and function of Treg from patients with ANCA-associated vasculitis (AAV). Methodology/Principal Findings Blood samples from 19 untreated patients with AAV during flares and before any immunosuppressive treatment were analyzed, along with 15 AAV patients in remission and 18 age-matched healthy controls. DC and Treg numbers, and phenotypes were assessed by flow cytometry, and in vitro suppressive function of Treg was determined by co-culture assay. When compared to healthy volunteers, absolute numbers of conventional and plasmacytoid DC were decreased in AAV patients. During the acute phase this decrease was significantly more pronounced and was associated with an increased DC expression of CD62L. Absolute numbers of Treg (CD4+CD25highCD127low/− Tcells) were moderately decreased in patients. FOXP3 and CD39 were expressed at similar levels on Treg from patients as compared to controls. The suppressive function of Treg from AAV patients was dramatically decreased as compared to controls, and this defect was more pronounced during flares than remission. This Treg functional deficiency occurred in the absence of obvious Th17 deviation. Conclusion In conclusion, these data show that AAV flares are associated with both a decrease number and altered phenotype of circulating DC and point to a role for Treg functional deficiency in the pathogenesis of AAV.
Antisynthetase syndrome belongs to the idiopathic myositis group which includes pulmonary interstitial disease, arthritis, Raynaud's phenomenon, and mechanic's hands , associated with the anti-Jo1 antibody. We report three cases of antisynthetase syndrome, and review the clinical characteristics, and prognosis factors dominated by interstitial pneumonia.
Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services.An Excel table-based survey was created to capture information on the laboratory's location and was emailed to 55 individuals with known or possible HNA investigation activity. The collected data were then summarized and analysed.Of contacted laboratories, the surveys were returned from 23 (38.2%) laboratories; 17 have already established HNA diagnostic (of them 12 were regular participants of the International Granulocyte Immunobiology Workshop [ISBT-IGIW]), 4 laboratories were in the process of establishing their HNA investigation and the remaining 2 responder laboratories, did not conduct HNA investigations. In established laboratories, investigation for autoimmune neutropenia (infancies and adults) was the most frequently requested, and antibodies against HNA-1a and HNA-1b were the most commonly detected.The directory of survey respondents provides a resource for health professionals wanting to access HNA diagnostic services. The present study offers a comprehensive picture of HNA diagnostics (typing and serology), identifying weak points and areas for improvement for the first time. Identifying more laboratories involved in HNA diagnostics with limited access to international societies in the field will globally improve HNA diagnostics.
Abstract. Antineutrophil cytoplasmic antibodies (ANCA) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Because autoantibodies may be directed against antigens presented by apoptotic cells, generation of ANCA using apoptotic neutrophils (PMN) in syngenic Brown Norway (BN) rats was attempted. These rats are T-helper type 2-prone animals, already used successfully in other ANCA-positive animal models. BN rats received repeated injections of buffer or of nonapoptotic or apoptotic PMN aged in cultures, in the footpad and once intravenously. Four of five rats that received injections of PMN aged for 48 h developed ANCA, which cross-reacted with human leukocyte elastase in three cases. None of the rats that received injections of freshly isolated neutrophils developed ANCA. One rat that received buffer injection and that exhibited chronic skin infection developed delayed ANCA. None of the rats showed signs of disease: no weight loss and no proteinuria. Then a subnephritogenic dose of antibody directed against rat glomerular basement membrane was injected. Rats then were killed, and different organs were frozen and studied. No significant lesions were found in kidneys or lungs. It is concluded that injections of apoptotic but not freshly isolated PMN can generate ANCA in BN rats. Additional studies are needed to elucidate the immunization mechanism and the ability of these autoantibodies to initiate vasculitis in these experimental animals.
