TARC and MDC Are the Only Chemokines with Highly Increased Levels in Serum of Hodgkin Lymphoma Patients.

Chemokines (cytokines with chemoattractant properties) can recruit different subsets of cells and therefore play an important role in the formation and maintenance of the non-neoplastic reactive infiltrate present in Hodgkin lymphoma (HL). The infiltrate consisting of lymphocytes, plasma cells, histiocytes and eosinophilic granulocytes is the most abundant part of the tumor mass in HL and surrounds the minority of neoplastic cells, the so-called Hodgkin-Reed Sternberg (HRS) cells. Several studies have shown that HRS cells and cells in the reactive infiltrate produce multiple chemokines. Especially TARC (CCL17) and MDC (CCL22) are highly produced by HRS cells. Altered serum chemokine levels might be related to HL prognosis or disease activity, since immunological mechanisms are crucial in HL pathogenesis. So far, only TARC and IL-8 levels have been studied in the serum of HL patients. In this study serum levels of nine chemokines including, Eotaxin, Fractalkine, IP10, MCP1, MDC, Mig, MIP1a, RANTES, and TARC were examined in serum of 163 untreated HL patients and 334 healthy controls using ELISA. In a subset of nine patients we also examined serum chemokine levels after treatment. Serum levels of TARC and MDC were significantly increased in 82% and 57% of the HL patient group compared to 12% and 5% in the control group, respectively. Serum Fractalkine and Mig levels did not show a difference between patients and controls, whereas serum levels of Eotaxin, IP10, MCP1, MIP1a, and RANTES were significantly decreased in HL patients. Analysis of the different subtypes revealed that the Nodular Sclerosis (NS) cases contained increased serum TARC and MDC levels compared to the Mixed Cellularity (MC) cases (p-value= 0,000). Serum TARC levels strongly correlated with serum MDC levels (r=0.82, p<0.01). Of the nine patients with serum samples before and after treatment, seven showed decreased serum TARC and MDC levels after treatment. One patient with increased levels before treatment did not show decrease in chemokine levels after treatment and died of disease. The last patient did not have increased chemokine levels before treatment and showed similar low levels in both serum samples. The other chemokines did not show a difference in serum levels in the before and after treatment samples. This is the first study testing a broad set of chemokines in serum of HL patients. Of all chemokines tested, TARC and MDC were the only chemokines with increased serum levels in the vast majority of HL patients and these can be used to monitor treatment efficiency.