Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes

Abstract

In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3 ؉ ) and T-helper cells (CD4 ؉ ) and a higher proportion of naïve CD4 ؉ CD45RA ؉ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 ؉ ) and the CD8 (CD11a ؉ ) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children

“…The collected results are consistent with the earlier finding regarding lymphocyte activation [34]. Maintained levels of TGF-b mRNA expression taken together with increased IL-4 and IL-10 expression makes it possible to assume that it could be Tr1 cells that are active in this tolerance maintenance.…”

“…Previous results from our ECP trial also showed that treated individuals had increased levels of IL‐10 compared with placebo controls [27]. Additionally, there was an indication that activated CD4 + and CD8 + cells increased in the placebo controls during the course of the study, an increase that was not observed in the actively treated group [34].…”

Abnormal Distribution of Gamma-Delta T Lymphocytes and Their Subsets in Type 1 Diabetes

“…In the present study, the size of T γδ populations in T1DM group ranged between 0.45% and 23.13%, was significantly (p = 0.042) lower than in healthy controls (4.1%-27.34%) and comparable to the level reported by Ernerudh [18]. Our observa- Control group tion could be explained by studies showing in NOD mice that a decreased level of T γδ cells caused diabetes development and the expansion of T γδ CD4 -CD8 + cells after aerosol insulin treatment was highly protective against auto aggression [6,19,20].…”

Guidelines on the use of extracorporeal photopheresis

“…However, in the placebo group, the proportions of activated CD4 + and CD8 + cells increased over time, whereas such changes were not seen in the ECP‐treated group. These findings probably reflect an activation of lymphocytes as part of the natural course of T1D and that ECP may have some suppressant effects, preventing lymphocyte activation . ECP produced cytokine changes reflecting a Th2‐like response .…”