Case Reports in Immunology最新文献

Mucosal melanoma accounts for 1% of all melanomas. It is more aggressive than cutaneous melanoma, and local excision provides the best disease-free survival. The vast majority of patients eventually develop metastases, with a metastatic pattern independent of the primary tumor site. While studies show that BRAF and KIT inhibitors have a role in the management of these patients, the actual treatment focus is on immunotherapy. Herein is described the case of a 79-year-old woman with metastatic mucosal melanoma and bone marrow infiltration causing disseminated intravascular coagulation, who was treated with an immunotherapy combination (anti-CTLA-4 and anti-PD-1 antibodies), achieving complete disease remission. This is the third case of melanoma with disseminated intravascular coagulation at presentation and the second case treated with immunotherapy in the literature, but the only one achieving disease remission.

Elevated IgE has been long recognized as an important clinical marker of atopy but can be seen in a myriad of conditions. The discovery of autosomal dominant STAT3 deficiency marked the first recognition of hyper-IgE syndrome (HIES) and the first primary immunodeficiency linked to elevated IgE. Since then, genomic testing has increased the number of defects with associated mutations causing hyper-IgE syndrome and atopic diseases with FLG, DOCK8, SPINK5, and CARD11, among others. A spectrum of recurrent infections and atopy are hallmarks of elevated IgE with significant phenotypic overlap between each underlying condition. As treatment is predicated on early diagnosis, genomic testing is becoming a more commonly used diagnostic tool. We present a 6-year-old male patient with markedly elevated IgE and severe atopic dermatitis presenting with staphylococcal bacteremia found to have a heterozygous variant in FLG (p.S3247X) and multiple variants of unknown significance in BCL11B, ZAP70, LYST, and PTPRC. We review the genetic defects underpinning elevated IgE and highlight the spectrum of atopy and immunodeficiency seen in patients with underlying mutations. Although no one mutation is completely causative of the constellation of symptoms in this patient, we suggest the synergism of these variants is an impetus of disease.

We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells. The patient was started on prednisone and tried several immunosuppressive medications including mycophenolate mofetil, methotrexate, hydroxychloroquine, and azathioprine with decrease in size of the orbital pseudotumor. During a period when the patient stopped his medications, the pseudotumor enlarged with new development of recurrent pleural effusions. He was also found to have a pelvic mass that was biopsy positive for IgG4 proliferation. This case with progression to multiorgan involvement highlights the importance of identifying patients with IgG4-related disease. In contrast to previous cases with normal-to-high IgM, the IgM was low with impaired functional antibodies.

Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. The syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G > T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome.

Background: NLRP3 gene is located in chromosome 1 and encodes a pyrin-like protein. Mutations in this gene are associated with an autoinflammatory disease, called cryopyrin-associated periodic syndrome (CAPS). Case Presentation. We report a 1-year-old boy who had recurrent urticarial rash since birth and joint pain and swelling. He had a missense mutation c.G1060 T (p.A354S) in exon 5 of the NLRP3 gene which was detected by whole exome sequencing.

Conclusion: A novel variant was found in the NLRP3 gene which has not been reported by now.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare X-linked disorder caused by a loss of function mutation in the FOXP3 gene. It manifests early in infancy with clinical symptoms including autoimmune enteropathy, type 1 diabetes mellitus, and eczema. While aberrant FOXP3 expression has been associated with several types of cancer, little is known regarding the risk of cancer in patients with IPEX harboring the characteristic FOXP3 mutation. Here, we present a unique case of a primary signet ring gastric adenocarcinoma in a pediatric patient with IPEX syndrome.

Zeta-chain-associated protein kinase 70 (ZAP-70) plays an integral role in the T-cell antigenic receptor complex. A deficiency of this kinase leads to a phenotype of severe combined immunodeficiency, while hypomorphic mutations of the kinase lead to more mild immunodeficiency phenotypes. We present a case of a 21-year-old patient with lymphadenopathy who was found to have Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) and the development of hemophagocytic lymphohistiocytosis (HLH). On further workup, the patient was ultimately found to have a homozygous intrionic mutation in ZAP-70. This is a novel ZAP-70 mutation (c.1623 + 5G > A) associated with combined immunodeficiency and an EBV-positive LPD. A primary immunodeficiency is important to consider in a young, otherwise healthy patient presenting with an EBV-positive LPD.

Extracorporeal membrane oxygenation (ECMO) is often used in the management of COVID-19-related severe respiratory failure. We report the first case of a patient with COVID-19-related ARDS on ECMO support who developed symptoms of heparin-induced thrombocytopenia (HIT) in the absence of heparin therapy. A low platelet count of 61 G/L was accompanied by the presence of circulating HIT antibodies 12 days after ECMO initiation. Replacement of the ECMO system including cannulas resulted in the normalization of the platelet count. However, the clinical situation did not improve, and the patient died 9 days later. Careful consideration of anticoagulant therapy and ECMO circuit, as well as routine HIT antibody testing, may prevent a fatal course in ECMO-supported COVID-19 patients.

Selective IgM deficiency (SIgMD) and isolated collagenous gastritis are two independent rare disorders. Our purpose is to report the 1^st case of SIgMD and isolated collagenous gastritis and collagenous gastritis that has transitioned to EBV + gastric adenocarcinoma. Gastric biopsy tissue was analyzed by EBV-related encoded RNA in situ hybridization assay. Subsets of CD4, CD8, T follicular helper cells (T_FH), and members of the "regulatory lymphocytes club" were measured with multiple panels of monoclonal antibodies and isotype controls by multicolor flow cytometry. The patient was diagnosed with SIgMD (extremely low serum IgM 9 mg/dl and normal IgG and IgA and exclusion of secondary causes of low IgM). Soon after SIgMD diagnosis, the patient developed collagenous gastritis and, 8 years later, developed gastric adenocarcinoma that was positive for EBV. An extensive immunological analysis revealed reduced naïve CD4 and CD8 effector memory T cells and increased naïve and central memory CD8 T cells. Among the circulating follicular helper T cells (cT_FH), T_FH1 and T_FH2 were increased whereas T_FH17 was decreased. CD4 Treg cells and T_FR cells were increased, whereas Breg and CD8 Treg were comparable to control. In conclusion, SIgMD may be associated with isolated collagenous gastritis, and collagenous gastritis may transition to EBV + gastric adenocarcinoma. A role of regulatory lymphocytes in gastric cancer is discussed.

Background: Henoch-Schönlein purpura (HSP) is an uncommon syndrome that mostly occurs in children, in whom it is frequently triggered by infections. In contrast, HSP in adults is more frequently of neoplastic origin. Case Presentation. We report HSP associated with a locally advanced lung squamous cell carcinoma that was considered a paraneoplastic syndrome. Systemic corticosteroids were given because a kidney biopsy revealed active glomerulonephritis. Concomitant chemoradiotherapy achieved a partial response of the lung tumor. Consolidation immunotherapy (programmed death protein-1-ligand-1 (PD-L1) inhibitor) was cancelled because HSP is known to be an autoimmune vasculitis, and long-term corticosteroid therapy was pursued.

Conclusion: Further prospective studies are needed to evaluate the effect of anti-PD-(L) 1 immunotherapies on autoimmune manifestations.