Pattern of T-Lymphocyte Subpopulation in Patients with Cold Agglutinin Disease

BACKGROUND. Cold agglutinin disease (CAD) is an orphan hematologic disease characterized mainly by hemolytic anemia, increased titer of cold antibodies, and clonality of B-lymphocytes in peripheral blood or/and bone marrow. The role of T-cell population imbalance in CAD has not been studied due to the rarity of this disease and extreme heterogeneity of its clinical and laboratory manifestations.

AIM. To analyze the pattern of T-lymphocyte subpopulation in CAD patients and to assess the information value of immune parameters for predicting the treatment efficacy and relapse risk.

MATERIALS & METHODS. Over the period from 2020 to 2023, 128 patients with autoimmune hemolytic anemia were examined and treated at the National Research Center for Hematology, the CAD diagnosis was confirmed in 25 of them. The control group consisted of 57 healthy blood donors.

RESULTS. Primary CAD patients showed significant decrease of naïve and central memory T-cells compared to similar subpopulations in donors. In 3 and 6 months after completion of immunosuppressive therapy with rituximab, CAD patients had a significant increase of T-helpers and cytotoxic T-lymphocytes as well as a decrease of T-regulatory cells. Among T-helper subpopulations, an increase in Th2 and Th17 cells was reported. The patients who achieved complete hematologic response prior to rituximab therapy, demonstrated a significant increase in Th22 cells. After 3 months of treatment, non-responders showed a drastic increase in cytotoxic T-lymphocytes followed by a decrease to baseline.

CONCLUSION. The analysis of the phenotypic spectrum of T-cells demonstrated the difference between the count of naïve and central memory T-cells in CAD patients and healthy donors. This study revealed no significant association of these parameters with the response to immunosuppressive therapy. The only factor associated with achieving complete hematologic response to rituximab was a higher Th22 baseline level compared to donor population.

• Polina Igorevna Vasilchenkova National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-0837-5603 (unauthenticated)
• M.N. Finyakina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0009-0001-3317-5718 (unauthenticated)
• O.F. Nikulina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0001-8123-7648 (unauthenticated)
• N.V. Tsvetaeva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-0977-215X (unauthenticated)
• S.M. Kulikov National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-6288-7570 (unauthenticated)
• I.V. Galtseva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-8490-6066 (unauthenticated)
• E.A. Lukina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-8774-850X (unauthenticated)

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