X-Linked Hyper IgM Syndrome Manifesting as Recurrent Pneumocystis jirovecii Pneumonia: A Case Report.

We reported a Chinese boy with X-linked hyper IgM (XHIGM) syndrome, manifesting as recurrent and severe pneumonia caused by Pneumocystis jirovecii. His parents were healthy and unrelated. In August 2018, the 5-month-old boy manifested as cough and dyspnea, and then in July 2019, he was admitted because of the same symptoms. Immunological results of the two admissions both showed low IgG, low IgA, normal IgM and high levels of 1,3-ß-D-glucan (BDG). Using next-generation sequencing (NGS), great reading counts of P. jirovecii were identified from the deep sputum in both admissions. Caspofungin combined with trimethoprim-sulfamethoxazole were used to anti-infection, and he recovered quickly. Whole-exome sequencing was performed for this family because of immune suppression, the disease-causing gene (exon 10-22 of CD40L) deletion for XHIGM syndrome was identified. NGS is beneficial for etiology diagnosis. Pneumocystis jirovecii pneumonia as an opportunistic infection could be recurrent in patients with XHIGM syndrome.

CD40 agonist antibody mediated improvement of chronic Cryptosporidium infection in patients with X-linked hyper IgM syndrome.

X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist monoclonal antibody, in the treatment of two XHM patients with biliary Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restoring class switch recombination in XHM B cells and inducing cytokine secretion by monocytes. CP-870,893 infusions were well tolerated and showed significant activity in vivo, decreasing leukocyte concentration in peripheral blood. Although specific antibody responses were lacking, frequent dosing in one subject primed T cells to secrete IFN-g and suppressed oocyst shedding in the stool. Nevertheless, relapse occurred after discontinuation of therapy. The CD40 receptor was rapidly internalized following binding with CP-870,893, potentially explaining the limited capacity of CP-870,893 to mediate immune reconstitution. This study demonstrates that CP-870,893 suppressed oocysts shedding in XHM patients with biliary cryptosporidiosis. The continued study of CD40 agonists in XHM is warranted.

[Progressive multifocal leukoencephalopathy]. / Progresszív multifokális leukoencephalopathia.

Progressive multifocal leukoencephalopathy is a rare disease caused by the reactivation of an opportunistic agent, JC virus almost in every cases in immunodeficient conditions. The disease is characterized by multifocal demyelinating lesions of the central nervous system and causes death within a few months. The authors report two patients: a 67 year-old male treated because of chronic lymphoid leukemia, and a 19 year-old male having a hereditary immunodeficiency, X-linked hyper IgM syndrome. In both cases continuously progressive right, later both hemispheric signs were detected. Cerebrospinal fluid was not helpful. Brain MRI showed bilateral large, white matter lesion. The progression was not influenced by the treatment, finally both patient died ten and six weeks after the appearance of first complaints. The diagnosis was confirmed by brain biopsy and autopsy in both cases. Our cases demonstrate that progressive multifocal leukoencephalopathy can develop in various immunodeficiencies.