Causal Impact of Immune Phenotypes on Herpes Zoster and Postherpetic Neuralgia: Insights from Mendelian Randomization Analysis

Abstract

Background: Previous research has investigated the contribution of immunological cells to both herpes zoster (HZ) and postherpetic neuralgia (PHN). This Mendelian randomization (MR) study seeks to further assess the cause-and-effect connection among 731 immune cell phenotypes and HZ and PHN providing partial causal evidence.

Methods: The data for HZ and PHN were sourced from the FinnGen database, and the 731 immune cell phenotypes were drawn from GWAS. Five analytical methods, primarily utilizing the inverse variance weighted (IVW) approach, were selected to assess the cause-and-effect connection in relation to exposure and outcomes. Finally, sensitivity analyses were undertaken to verify the robustness as well as validity of the data.

Results: The MR analysis utilizing the IVW method revealed that in the forward Mendelian randomization, two immune cell phenotypes of T cells were negatively connected with HZ(P < 0.05, OR < 1). In comparison, two other immune cell phenotypes were advantageously linked with PHN(P < 0.05, OR > 1). In the reverse Mendelian randomization, HZ was positively associated with five immune cell phenotypes from T cells and NK cells (P < 0.05, OR > 1). PHN demonstrated a positive association with nine immune cell phenotypes from T cells, myeloid cells, B cells, CDC, and monocytes (P < 0.05, OR > 1), while showing a negative association with the remaining 11 immune cells (P < 0.05, OR < 1). Likewise, No evidence of disparity, horizontal pleiotropy, or backward causality was found.

Conclusion: This study employs Mendelian randomization analysis to elucidate the complex causal relationships between various immune cell phenotypes and the development of HZ and PHN. The findings provide insights into the immune mechanisms underlying disease progression, advancing our understanding of immune-mediated pathways and their potential implications for future therapeutic strategies.

Keywords: Mendelian randomization; causal effect; herpes zoster; immunophenotypes; postherpetic neuralgia.

Figure 1

Plot of key assumptions for MR analysis.

Figure 2

Forest plots showed the causal associations between immune cell phenotypes and HZ by using different methods.

Figure 3

Forest plots showed the causal associations between immune cell phenotypes and PHN by using different methods.

Figure 4

Forest plots showed the causal relations between HZ and immune cell phenotypes.

Figure 5

Forest plots showed the causal relations between PHN and immune cell phenotypes.