Clinical Immunology Communications最新文献

Deficiency of Interleukin-1 receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory disease first reported in 2009. To date, 33 patients have been previously characterized and reported in literature. To the best of our knowledge, there have been no recent studies that have broadly evaluated recent advances in understanding of this challenging and life-threatening condition. Herein, we comprehensively reviewed the etiology and cytogenetic abnormalities of DIRA. We then investigated the current diagnostics used for identifying the variants of this disease. Furthermore, we report the demographics and characteristics broadly found in the current patient sample. Lastly, we discuss the treatments (antibiotics, corticosteroids, etc.) and the primary biologics (anakinra, canakinumab, adalimumab, and rilonacept) used in patients, along with current information on their clinical safety and efficacy. Overall, although further investigations are required for this disease, this review may be informative to clinicians treating and managing patients presenting with DIRA.

Chronic granulomatous disease (CGD) is an inborn error of immunity. NADPH oxidase is an enzyme complex that produces various reactive oxygen species, such as superoxide anions and hydrogen peroxide. Mycobacterial infections in CGD are commonly observed in countries with a high prevalence of these microorganisms, such as those receiving the BCG vaccination at birth or having a high prevalence of tuberculosis. Non-tuberculous mycobacteria (NTM) infections are rare in CGD. The patient also presented with hemophagocytic lymphohistiocytosis, which resolved with gammaglobulin and cyclosporine. Herein, we describe the first case of M. chimaera infection in a female patient with autosomal recessive CGD caused by a pathogenic variant in CYBA.

We present an interesting case of a 65-year-old female patient who was taking fingolimod for relapsing-remitting multiple sclerosis. She presented with a tongue nodule, oral ulcer, and was found to have CD4 lymphocytopenia. HIV serology was negative. Fingolimod is known to cause lymphocyte redistribution to lymph nodes and was deemed to be the cause of CD4 lymphocytopenia in this patient. Further evaluation with excision biopsy of the tongue nodule confirmed histoplasmosis. Treatment with itraconazole resulted in a complete resolution of her lesions.

Multisystem Inflammatory Syndrome in Adults (MIS-A) is a rare complication after COVID-19 that mainly occurs in young adults. Patients typically present with unremitting fever, rash, conjunctivitis, neurological signs, shock, gastrointestinal symptoms and thrombocytopenia. Reported cases are scarce. Here we describe three new cases.

It is unclear to what extent MIS-A has a genetic basis, or whether MIS-A patients can be safely vaccinated after a case of MIS was reported after vaccination (termed MIS-V). We describe a monozygotic twin who was vaccinated without complications, suggesting no strict genetic basis for MIS-V. Furthermore, we report only the second case of MIS-A-related coronary aneurysm, which fully resolved upon regular treatment.

With the majority of young adults living in low resources settings, we suggest more focus on clinical parameters to support a MIS-A diagnosis. We report the first two patients of North-African descent. Currently, MIS-A may be an underappreciated complication of COVID-19 due to the lack of reports in non-Caucasian populations.

Immunological dysfunction in multiple lineages of hematopoietic cells and mixed chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with an increased risk of autoimmunity in patients with Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). Here, we report the efficacy of rituximab against autoimmunity in five patients with WAS and XLT. One patient with systemic arthritis and vasculitis, and two patients with immune thrombocytopenia were successfully treated with rituximab before initiating reduced-intensity conditioning. Rituximab was also used in combination with conditioning to prevent autoimmunity by depleting the recipient B cells in the other two patients with XLT. None of the patients developed autoimmunity without delay in donor B cell reconstitution, even though two patients had stable mixed chimerism after HSCT. These results suggest that aberrant B cell-intrinsic mechanisms are a central cause of autoimmunity, and rituximab is an effective therapeutic option for autoimmunity in patients with WAS and XLT.

Acquired hemophilia A is a rare but serious bleeding disorder that occurs because of neutralizing autoantibodies, also called inhibitors that target coagulation factor VIII (FVIII). Although it is a rare disorder, it has high morbidity and mortality with serious, sometimes life-threatening bleeding, often occurring. Immunotherapy with immune checkpoint inhibitors (ICI) is now a key pillar in treatment of malignancies. They have improved outcomes in malignancy but given their mechanism of action, which stimulates the immune response, autoimmune-associated adverse effects are a concern. Several case reports have identified a risk of AHA occurrence in patients treated with ICI. There are no case reports documenting the use or outcomes of ICI in patients with pre-existing AHA. Here we present the first ever case of a patient with AHA in complete remission treated successfully with ICI for lung cancer without relapse in AHA.

Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) is a monogenic autoimmune disease most often resulting from biallelic loss-of-function variants in the autoimmune regulator (AIRE) gene. Although typically characterized by the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, we have recently reported that the clinical spectrum of the syndrome is far broader that previously described and that incorporation of an adjunct triad of APECED rash, autoimmune enteritis-associated intestinal dysfunction, and enamel hypoplasia in the classic triad manifestations could lead to earlier diagnosis. Among the adjunct triad manifestations, APECED rash occurs in 66 % of American APECED patients by age 3, most often developing in the first year of life. Here, we describe the clinical and histological features of protracted APECED rash manifesting together with recurrent mucocutaneous candidiasis as the first two disease components of APECED in a 10-month-old girl.

Syndrome of Congenital Sideroblastic Anemia, B-cell Immunodeficiency, Periodic Fevers, and Developmental Delay (SIFD) is caused by mutations in the tRNA nucleotidyltransferase 1 (TRNT1) gene. We present the case of a 13-month-old boy with developmental delay, microcytic anemia, and recurrent febrile illnesses. Immunological workup revealed B cell lymphopenia. Whole exome sequencing identified two novel heterozygous mutations in the TRNT1 gene (Thr49Fs and Ile122Thr). Our patient had a milder phenotype than previously reported cases of sideroblastic anemia. However, he developed left ventricular dilated cardiomyopathy at the age of 2 years. At the age of 5 years, COVID-19 infection resulted in mitochondrial encephalomyopathy and respiratory failure. Subsequent immunology evaluation revealed low IgG levels, prompting the initiation of immunoglobulin replacement therapy. This case highlights the importance of genetic testing in multisystem disorders and the variable clinical course in SIFD patients. Additionally, it emphasizes the unique susceptibility to COVID-19 due to immunodeficiency and mitochondrial defects.

This study investigates HLA-DR expression on activated T cells and serum neopterin levels in Juvenile Dermatomyositis (JDM) children pre- and post-treatment. Sixty-nine JDM children (less than 18 years) were included. Elevated HLA-DR+ T cells (>7 %) were observed in 19 % of untreated cases. Post-treatment, mean HLA-DR+ T cells decreased from 5.1 to 2.9 (P < 0.001), and serum neopterin levels declined from 19.3 to 9.1 nmol/L (P < 0.0001). A positive correlation between serum neopterin and HLA-DR T cell percentage was observed (r = 0.39, P = 0.01). Intravenous steroid treatment exhibited a 47.4 % improvement in HLA-DR+ T cells and a 50.5 % reduction in serum neopterin levels, in contrast to 14.8 % and 34.1 % in the oral steroid group. In conclusion, treatment, particularly with IV steroids, significantly improved HLA-DR+ T cells percentage and neopterin levels. A correlation between HLA-DR+ T cells percentage and serum neopterin was noted in untreated JDM patients.

Good syndrome (GS) is a combined immunodeficiency that is associated with thymomas. The cause of the reduction in B-cells in patients with GS may be multifactorial and may include dysregulated T-cell responses. It has been proposed that tumorigenesis in a normal thymus alters thymic epithelial cell function, which leads to attenuated elimination of T-cells autoreactive to B-cells. Although the comprehensive genetic analysis of thymoma has been performed and reported in many articles, the comprehensive genetic analysis specified for GS-related thymoma has not been reported. Herein, we report comprehensive genetic analysis of a thymoma taken from a patient with GS. Oncogenesis-associated genes that may contribute to thymoma development were detected. Additionally, alteration of VCAM1, which is required in the interaction between T-cells and thymic epithelial cells, was observed. Aberrantly expressed VCAM1 in thymic epithelial cells may decrease the efficacy of negative of selection autoreactive T-cells and contribute to autoimmunity to B-cells.