anti-tetanus immunoglobulin (Tetglob)

CD19, immunoglobulin level, and varied anti-cytokine autoantibodies underline dichotomous susceptibility to types of infection in patients with thymomas.

Tan Zhaohong Z, Shin Areum A, Tan Rachel Ying Min RYM, Wang Dongling D et al.

Increased susceptibility to infections is observed in patients with thymomas. These have been invariably attributed to Good syndrome with hypogammaglobulinemia, but there is noticeable heterogeneity in clinical presentation. We clinically and immunophenotypically characterized the infective susceptibilities encountered in these patients. Of thymoma patients recruited from Singapore and South Korea, their infection types were correlated against immunological parameters, including IgG, IgM, IgA, CD19+ B cells, and CD4+ T cells, and the presence of neutralizing anti-cytokine autoantibodies using direct ELISA. Lymphocyte subset immunophenotyping was performed. Ascertainment of immune signaling pathway disruption was through serum switch experiments. Respective immune signal outputs were probed using Western blotting. A total of 15 thymoma patients (median age, 54 years; 13 men [87%]) were clustered into two groups with discernible differences in infective manifestations. In one group, nine patients (60%) had recurrent/severe viral or Pneumocystis jirovecii infections. These patients had low immunoglobulins and CD19+ B cells. The second group of six patients (40%) had difficult-to-treat non-tuberculous mycobacterium (NTM) or invasive bacterial or fungal infections. They had normal immunoglobulins levels and possessed autoantibodies against interleukin (IL-)-12, IL--23, or interferon-alpha (IFN-α), which consisted of anti-IFN-α2 and anti-IFN-ω subtypes. The autoantibodies consisted of a heterogeneous spread across IgG1 to IgG4 subclasses. These anti-IL--12, anti-IL--23, and anti-IFN-α autoantibodies were neutralizing and compromised various phosphorylated-STAT signaling pathways that are critical in host anti-pathogen response. The dichotomy of infective manifestations (viral/PJP versus NTM/invasive bacteria/fungal) underlies distinct and novel immune susceptibility beyond the classic Good syndrome label in thymoma patients, with implications for different approaches to clinical management.

A Rare Case of Plasmablastic Myeloma With Dual Kappa and Lambda mRNA Expression Presenting as a Solitary Hard Palate Tumor.

Tanaka Ken K, Hasegawa Masaki M, Katsumi Akira A

Plasmablastic myeloma is an aggressive variant of plasma cell myeloma that can mimic plasmablastic lymphoma when it presents as a solitary mass. Dual kappa and lambda light-chain expression is exceptionally rare and may be missed if evaluation relies on protein-level detection alone. We report the case of a woman in her 80s who presented with left hard palate swelling and underwent resection of a solitary hard palate and maxillary tumor. Histology showed sheets of large plasmablastic cells positive for CD38, CD138, multiple myeloma oncogene 1, and immunoglobulin G, and negative for B-cell markers and Epstein-Barr virus-encoded RNA. Within weeks, she developed malaise, nausea, and pancytopenia. Laboratory studies revealed elevated lactate dehydrogenase and serum immunoglobulin G of 4,409 mg/dL with immunoparesis. Serum free light chains showed mildly elevated kappa and markedly elevated lambda, with a kappa/lambda ratio of 0.02. Positron emission tomography-computed tomography demonstrated diffuse skeletal and splenic fluorodeoxyglucose uptake without additional extramedullary lesions, confirming the hard palate tumor as the only extramedullary site. Bone marrow examination showed marked hypercellularity with extensive replacement by plasmablastic plasma cells expressing cyclin D1, while Epstein-Barr virus studies and anaplastic lymphoma kinase were negative. Light-chain immunohistochemistry showed absent kappa staining and lambda staining in only a small subset of tumor cells, whereas RNA in situ hybridization demonstrated dual light-chain messenger RNA expression in most tumor cells. Cytogenetic analysis revealed 1q21 amplification, deletion of 17p13, and immunoglobulin heavy chain/MAF rearrangement. Despite high-dose dexamethasone, sequential proteasome inhibitor-, anti-CD38 antibody-, and immunomodulatory drug-based therapies, followed by B-cell maturation antigen × CD3 bispecific antibody treatment, the disease remained refractory and the patient died 45 days after diagnosis. This case highlights that transcript-based light-chain testing can uncover exceptionally rare dual kappa and lambda expressions when protein assays are negative or misleading. In solitary plasmablastic lesions, integrated clinicopathological assessment, including cyclin D1, Epstein-Barr virus studies, and RNA in situ hybridization, is critical for accurate diagnosis and recognition of this highly aggressive subtype.

Sibeprenlimab (Voyxact) for primary immunoglobulin A nephropathy.

Reappraising the role of procalcitonin in predicting intravenous immunoglobulin resistance in Kawasaki disease.

Kundavaram Rajkumar R, Kumar Amber A