Background/Purpose: Lymphocytes from rheumatoid arthritis (RA) patients have been reported to exhibit increased basal intracellular Ca²⁺ concentrations compared with the lymphocytes of healthy controls.  A precise molecular explanation for the enhanced Ca²⁺ influx in T cells has not yet been established. To explore the molecular basis of the irregular Ca²⁺ influx in RA T cells, we performed a cross-sectional study to characterise the expression levels and functional status of Ca²⁺ release-activated Ca²⁺ (CRAC) channels in peripheral naïve CD4⁺ T cells from 50 RA patients, 50 osteoarthritis (OA) patients and 15 healthy donors.

Methods: To determine whether CRACM1 channels contribute to the abnormal behavior of T cells in RA, CRACM1 expression was evaluated by western blotting and immunofluorescence analysis. We also measured Ca²⁺ influx and CRAC currents in naïve CD4⁺ T cells, as well as cytokine release by activated naïve CD4⁺ T cells, for each of the three groups.

Results: 1.Intracellular Ca²⁺ influx is up-regulated in naïve CD4⁺ T cells from RA patients and is associated with RA disease activity.2 .CRACM1 channel function is increased in T cells from active RA patients. 3.CRACM1 expression in naïve CD4⁺ T cells is higher in active RA patients than in OA patients and healthy donors.  

 Conclusion: Functionally aberrant naïve CD4⁺ T cells from active RA patients exhibited an increase in Ca²⁺ influx, as well as up-regulated CRACM1 protein expression and function, indicating that CRACM1 might represent a new molecular target for novel RA therapies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/enhancement-of-cracm1-expression-in-functionally-aberrant-naive-cd4-t-cells-in-active-rheumatoid-arthritis/