Case Reports in Immunology最新文献

We present the case of a 24-year-old male, who received a minor ABO-incompatible allogeneic hematopoietic stem cell transplant (HSCT, blood group O⁺ ⟶ A⁺) from an HLA-matched unrelated female donor, as consolidation therapy for relapsed precursor-B-cell acute lymphoblastic leukemia. The donor had a known history of Hashimoto's thyroiditis before HSCT. At day +10 posttransplant, the patient developed severe hemolysis, which required emergent red blood cell exchange. Additionally, about a year posttransplant, he had circulating antithyroglobulin antibodies, decreased free-T4 (fT4) and increased serum thyroid-stimulating hormone (TSH). The potential causes of the posttransplant hemolytic episode and hypothyroidism are discussed. While the hemolysis was worsened by the transfusion of A red blood cells (RBCs) in the context of passenger lymphocyte syndrome, the thyroid dysfunction might be explained by an autoimmune disease transferred from the donor. The case highlights the possibility of several non-relapse-related complications of HSCT occurring in the same patient. It is critical that such adverse outcomes are distinguished from classical graft-versus-host disease (GVHD) for adequate recipient counseling, posttransplant screening, and prompt treatment.

Agammaglobulinemia is a rare inherited immunodeficiency disorder. Mutations in the BLNK gene cause low levels of mature B lymphocytes in the peripheral blood leading to recurrent infections. We present a four-year-old Turkish boy who had recurrent respiratory tract infections in the last six months. He had very low IgG (81 mg/dl) and IgA levels (<5 mg/dl) with high IgM (258 mg/dl). Flow cytometric analysis of lymphocyte subsets showed low CD19+ B cells (0.05%). Homozygous c.790C > T (p.Gln264Ter) mutation was detected in the BLNK gene with Targeted Next Generation Sequencing (TNGS) gene analysis. Agammaglobulinemia may be due to different genetic etiologies together with complex genetic events. Although the first diagnosis to be considered in male patients is Bruton's agammaglobulinemia, patients with normal BTK sequence and/or expression should be investigated with a large genetic study such as TNGS in the early period to reach a definitive diagnosis. This male case of agammaglobulinemia highlights the necessity of considering BLNK mutations in children with B cell deficiency, even though they are known to be rare causes of agammaglobulinemia. Our case is also remarkable with high IgM levels before intravenous immunoglobulin replacement therapy and with late-onset severe infections.

The availability of next-generation sequencing (NGS) helps to resolve many of the diagnostic odysseys. Common variable immunodeficiency disease (CVID) is an entity encompassing a heterogenous group of conditions with hypogammaglobulinemia, and it is a diagnosis of exclusion. In recent years, with the advances of molecular diagnostics, more and more patients have been reclassified with more defined entities after their genetic causes were found. Here, we reported a young man, who was managed as CVID since childhood, presenting with recurrent infection, hypogammaglobulinemia, and immune thrombocytopenia (ITP). Finally, more than a decade after initial presentation, gene panel testing revealed a novel mutation in the MAGT1 gene. Collectively, the genetic findings and clinical presentations confirm the diagnosis of X-linked immunodeficiency with magnesium defect and Epstein-Barr virus infection and neoplasia (XMEN). MAGT1 is an evolutionarily conserved, magnesium-specific transporter expressed in all mammalian cells that plays an essential role in magnesium homeostasis. MAGT1 also acts as an accessory protein for STT3B, as catalytic subunits of the oligosaccharyltransferase protein complex, which carries out glycan chain transfer to proteins in the endoplasmic reticulum during N-glycosylation. Glycans play an essential role in the stability, maturation, and localization in glycoproteins that are important in our immune cells' function. Mutation of the gene resulted in a rare X-linked recessive condition XMEN. The disease has complete penetrance but variable expressivity. It is mainly associated with immunodeficiency, immunodysregulation, and predisposition to EBV-associated lymphoproliferation. Extraimmune manifestations have also been reported in some patient cohorts, including hepatic and neurological abnormalities. Overall, the presentation varies among patients and overlaps with other clinical entities, in which diagnosis is challenging. Before the era of NGS, traditional workup hinges heavily on phenotype studies, followed by single-gene sequencing. The diagnostic yield is low, and a significant delay in diagnosis is common. This case illustrated the importance of early consideration of molecular studies in complex immunological cases without obvious secondary causes as an integral part of patient management.

We share our experience of a patient with pulmonary alveolar proteinosis who was refractory to plasmapheresis and rituximab despite a significant reduction in the offending antibody. He presented with shortness of breath, fevers, chills, and sweats for 4 months. He was diagnosed with autoimmune PAP based on typical radiology findings, bronchoalveolar fluid analysis, and elevated anti-GM-CSF levels. Given his limited improvement with whole lung lavage and inhaled GM-CSF therapy, he underwent two series of plasmapheresis. Series one was 5 procedures in 6 days, and series two was 5 procedures in 9 days followed by rituximab. These did not appear to provide any lasting clinical benefit in the year after plasmapheresis despite a marked decrease in serum anti-GM-CSF levels. However, about a year after plasmapheresis, he went into remission and has not required any treatment.

Paraneoplastic neurological syndrome (PNS) is associated with malignancies, including small-cell lung cancer. Recently, PNS cases among patients with small-cell lung cancer (SCLC) induced by immune checkpoint inhibitors have increased. We herein report a 66-year-old man with SCLC who developed disorientation, dysphagia, and gait disturbance after three courses of treatment with atezolizumab. Brain magnetic resonance imaging revealed a high-intensity area in the bilateral temporal lobes. Blood test results were positive for anti-Hu and anti-Zic4 antibodies, which led to the diagnosis of limbic encephalitis as PNS. Some symptoms improved with intravenous administration of steroids and immunoglobulins.

Background: PAPA syndrome (MIM #604416) is a rare monogenic autoinflammatory disease genetically transmitted in an autosomal dominant trait that results from missense mutations in the proline-serine-threonine phosphatase-interactive protein 1 (PSTPIP1) gene located on chromosome 15 and is characterized by sterile pyogenic arthritis, pyoderma gangrenosum, and cystic acne. We describe the clinical and molecular findings of two related Brazilian patients with PAPA syndrome. Case Presentation. A 7-year-and-3-month-old boy with nonconsanguineous parents had had recurrent pyoarthritis since the age of 5 years and 8 months. During his last and long hospitalization, the lack of improvement with antibiotics, evidence of increased inflammatory activity, repeated arthrotomies, draining purulent fluid that had negative cultures, and the history of trauma, all on in a clinical background of pyoarthritis, led to the suspicion of an autoinflammatory syndrome. This was confirmed by the good clinical response to corticotherapy. Genetic sequencing confirmed the diagnosis of PAPA syndrome, with the pathogenic mutation c.688 G > A (p. Ala230Thr) in the PSTPIP1 gene present in the patient and in the mother.

Conclusions: This case illustrates that in children with recurrent/recalcitrant sterile recurrent pyogenic arthritis/osteomyelitis, the possibility of an underlying immunological condition should be considered. In both, recurrent infections or recurrent inflammation, many genes involved in the inborn errors of immunity can be associated, and a correct and precocious diagnosis is necessary to avoid mobility and mortality. To the best of our knowledge, this is the first report of PAPA syndrome in Brazil.