Lymphocytes subsets in correlation with clinical profile in CVID patients without monogenic defects

ABSTRACT

Objectives: Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy, and lymphoproliferation. We evaluated the correlation of lymphocyte subpopulations with such manifestations.

Methods: Twenty-six genetically unsolved CVID patients were subdivided into four phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE), and lymphoproliferative disorders (LP) and examined for lymphocyte subsets by flow cytometry and TCD4⁺ proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test.

Results: We detected reduced memory B and increased total, effector memory (EM), cytotoxic, and activated TCD8⁺ in IO, AI and CE, decreased plasmablasts, total and naive TCD4⁺, Regulatory TCD4⁺ (Treg) and naive TCD8⁺ in IO and CE, elevated CD21^low B and terminally differentiated effector memory (T_EMRA) TCD8⁺ in IO and AI, increased helper T (Th2) and Th17 in IO, decreased Th1 in AI and defective total and naive B and central memory (CM) TCD4⁺ in CE. IO showed reduced TCD4⁺ proliferation response.

Conclusions: In genetically unsolved CVID patients, increased Th2 and Th17 and reduced Treg is associated with IO, increased CD21^low B and T_EMRA TCD8⁺ and reduced Th1 is contributed to AI and reduced total and naive B, CM TCD4⁺ and naive TCD8⁺ and expanded total TCD8⁺ is correlated with CE.

KEYWORDS:

• Primary immunodeficiency
• inborn errors of immunity
• common variable immunodeficiency (CVID)
• lymphocytes subsets
• clinical profile
• proliferation response

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Author contributions

FTZ was involved in the design of the study, collection, analysis and interpretation of the data, drafting of the paper and revising it. AM, RY, AAK, NR and HA were involved in the analysis and interpretation of the data; the drafting of the paper or revising it critically for intellectual content; and the final approval of the version to be published. YB, AR and SD were involved in the collection of the data. AA was involved in the conception and design of the study, analysis and interpretation of the data. All authors revised the paper critically for intellectual content and agreed to be accountable for all aspects.

Supplementary material

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Additional information

Funding

This paper was funded by Vice Chancellor for Research, Tehran University of Medical Sciences and Health Services, (1395-03-154-32597).