Publications by authors named "Alexander Leiss-Piller"

Article Synopsis
  • Trichothiodystrophy-1 (TTD1) is an autosomal-recessive disease linked to mutations in a gene important for DNA repair and transcription, leading to increased susceptibility to infections in affected patients.
  • The study examined the immune system and DNA repair capabilities of three TTD1 patients, revealing issues such as low antibody responses, problems with B-cell proliferation, and accumulation of DNA damage markers.
  • Findings indicated that TTD1 is associated with antibody deficiencies due to impaired B-cell development and function, confirming the impact of new mutations on the immune system.
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Suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) ER-associated degradation (ERAD) plays a critical role in many physiological processes in mice, including immunity, water homeostasis, and energy metabolism; however, its relevance and importance in humans remain unclear, as no disease variant has been identified. Here, we report a biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family.

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Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).

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Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy.

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X-linked lymphoproliferative disease (XLP1) is a combined immunodeficiency characterized by severe immune dysregulation caused by mutations in the gene. Loss or dysfunction of SH2D1A is associated with the inability in clearing Epstein-Barr-Virus (EBV) infections. Clinical manifestation is diverse and ranges from life-threatening hemophagocytic lymphohistiocytosis (HLH) and fulminant infectious mononucleosis (FIM) to lymphoma and antibody deficiency.

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Mutations of the interleukin 2 receptor γ chain (IL2RG) result in the most common form of severe combined immunodeficiency (SCID), which is characterized by severe and persistent infections starting in early life with an absence of T cells and natural killer cells, normal or elevated B cell counts and hypogammaglobulinemia. SCID is commonly fatal within the first year of life, unless the immune system is reconstituted by hematopoietic stem cell transplantation (HSCT) or gene therapy. We herein describe a male infant with X-linked severe combined immunodeficiency (X-SCID) diagnosed at 5 months of age.

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Variants in recombination-activating genes () are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency. We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the defects in populations inhabiting South, West, and East Slavic countries. Demographic, clinical, and laboratory data were collected from -deficient patients of Slavic origin via chart review, retrospectively.

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B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated patients that perturb the intrinsic B-cell receptor signaling pathway and lead to selective IgM deficiency, whereas production of other immunoglobulin isotypes and IgG antibody response remain intact.

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