bims-actimu Biomed News
on Actinopathies in inborn errors of immunity
Issue of 2026–02–15
three papers selected by
Elodie Busch, University of Strasbourg
  1. WAS Protein Deficiency Disrupts Memory B Cell Formation During Acute LCMV Infection.
  2. Heterozygous variants in DOCK2 leading to susceptibility to viral illnesses.
  3. Recurrent pyoderma gangrenosum-like ulcers in a child revealing leukocyte adhesion deficiency type I.
  1. J Clin Immunol. 2026 Feb 11.
    WAS Protein Deficiency Disrupts Memory B Cell Formation During Acute LCMV Infection.
    Liang Zhang, Yongjie Liu, Dujuan Zhou.
      Wiskott-Aldrich syndrome (WAS) is a rare x-linked monogenic immunodeficiency disease, caused by the mutation of WAS gene encoding WAS protein (WASp). Previous findings in WAS patients show B cell perturbations in the periphery, characterized by diminished B-cell numbers and phenotype abnormalities, including reduced frequency of classical CD27+ memory B cells (MBCs), accompanied by an unusual expansion of atypical CD21low MBCs. The mechanism underlying these abnormalities in MBCs developmental pathway has not been completely dissected. In this study, WASp knock-out mice undergone with acute lymphocytic choriomeningitis virus (LCMV) infection was used as a model to investigate the effects of WASp deficiency on the differentiation of MBCs and the possible mechanisms. We found that by day 11 after infection, the proportion of classical IgG2c+ MBCs was dramatically decreased, this was accompanied by a corresponding increase in the proportion of atypical CD21low MBCs. Using single-cell RNA sequencing (scRNA-seq), we also identified WASp deficiency promoted the formation of atypical MBCs during acute viral infection. Remarkably, our study revealed a marked reduction of WASp expression in atypical MBCs. Overall, our data show that WASp is differentially expressed in MBCs subsets, and manipulates the fate of MBCs during acute LCMV infection.
    Keywords:  Immunodeficiency; Wiskott-Aldrich syndrome; cell differentiation; memory B cells; scRNA-seq
    DOI:  https://doi.org/10.1007/s10875-026-01984-5
  2. J Allergy Clin Immunol. 2026 Feb 05. pii: S0091-6749(26)00080-1. [Epub ahead of print]
    Heterozygous variants in DOCK2 leading to susceptibility to viral illnesses.
    Amer Al-Musa, Craig Platt, Megan Elkins, Tanya Novak, Brian Woods, Aleksandra Bourdine, Logan Magin, Brittany G Craiglow, Margaret M Newhams, Michele Kong, Adrienne Randolph, Janet Chou.
       BACKGROUND: Inborn errors of immunity (IEIs) are classically identified in infants and young children with severe or recurrent infections. However, hypomorphic variants with a partial loss of function can remain unrecognized until later in life and may underlie clinically significant susceptibility to infections in previously healthy individuals.
    OBJECTIVE: We investigated how three novel heterozygous variants in DOCK2 contribute to impaired anti-viral immunity, extending the understanding of DOCK2 deficiency beyond an autosomal recessive disease.
    METHODS: After identifying the first DOCK2 variant, we screened 1,109 exomes from three cohorts of patients with a history of at least one severe respiratory, bloodborne, or soft tissue infection. We assessed the biologic impact of each variant via functional and transcriptional assays of the patients' primary peripheral blood mononuclear cells and in cell-based overexpression systems.
    RESULTS: Six individuals from three unrelated families, aged 3 months to 50 years, caried one of three heterozygous variants in DOCK2 and experienced severe infections with human papilloma virus, respiratory syncytial virus, or SARS-CoV-2. All variants reside within the DOCK2 domain that binds and stabilizes ELMO1. Each variant reduced DOCK2 protein expression, ELMO1 binding, and DOCK2 function, as shown by diminished Rac1 activation and selective defects in Toll-like receptor signaling. Weekly IFN-α therapy led to complete resolution of refractory warts in one patient, highlighting a potential therapeutic approach for DOCK2-associated immunodeficiency.
    CONCLUSIONS: These findings expand the spectrum of DOCK2-related disease by showing that heterozygous pathogenic variants disrupting DOCK2-ELMO1 interactions impair protein stability and anti-viral immunity, revealing a previously unrecognized IEI affecting otherwise healthy individuals.
    Keywords:  DOCK2; Immunodeficiency; anti-viral immunity
    DOI:  https://doi.org/10.1016/j.jaci.2026.01.026
  3. Clin Exp Dermatol. 2026 Feb 10. pii: llag063. [Epub ahead of print]
    Recurrent pyoderma gangrenosum-like ulcers in a child revealing leukocyte adhesion deficiency type I.
    Dipra Biswas, Debdatta Saha, Suman Patra, Deepak Vedant.
      
    DOI:  https://doi.org/10.1093/ced/llag063
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