Soluble CD40 ligand is not elevated in plasma of patients with chronic spontaneous urticaria

Funding sources: this study was supported by a research grant from the Committee for Scientific Research (KNW‐1‐130/P/1/0). Conflicts of interest: none declared. Madam, The interaction between CD40 and the CD40 ligand (CD40L) is involved in regulating both humoral and cellular immune response. CD40L is expressed by different cell types, including platelets, and it is subsequently cleaved, generating a circulating soluble form (sCD40L). Elevated circulating levels of sCD40L have been observed in a variety of inflammatory diseases where sCD40L is thought to promote proinflammatory effects.1 It has been demonstrated that the serum sCD40L level is significantly increased in chronic urticaria (CU).2, 3 This suggests that sCD40L may be involved in the immune activation observed in this disease.2 CD40L also shows some prothrombotic properties, and elevated plasma levels of sCD40L indicate increased risk for cardiovascular events in otherwise healthy women. Such observations should stimulate further evaluation of sCD40L in patients with urticaria. Serum CD40L levels might reflect best the total cellular CD40L content, whereas plasma CD40L might best reflect the level of the protein shed from circulating cells and is more likely to reflect the in vivo situation. Over 95% of the circulating CD40L exists in platelets, therefore platelet activity must be considered in the context of CD40L function. As platelets are a potential source of increased serum CD40L levels, using platelet‐poor plasma (PPP) is the best way to minimize the potential variable contribution of these cells to the actual CD40L level.4, 5 Therefore, in the present study, in order to assess free circulating CD40L in urticaria, the PPP level of CD40L in patients with CU with positive and negative responses to the autologous serum skin test (ASST) was investigated for the first time. Sixty‐seven patients with active spontaneous CU were enrolled in the study divided into two groups: (i) ASST‐negative CU group – 38 patients with a negative response to the ASST (23 female, 15 male; median age 38 years, range 20–45); and (ii) ASST‐positive CU group – 29 patients with a positive response to the ASST (16 female, 13 male; median age 36 years, range 20–42).