Differential Expression and Correlation of High-mobility Group Box 1 and Vascular Endothelial Growth Factor Messenger Ribonucleic Acid across Leprosy Clinical Groups and Healthy Controls: A Cross-sectional Study

Abstract

BACKGROUND: Erythema nodosum leprosum (ENL) is an acute inflammatory complication of multibacillary leprosy. High-mobility group box 1 (HMGB1) mediates inflammatory signaling, whereas vascular endothelial growth factor (VEGF) regulates angiogenesis and vascular permeability. We compared whole-blood HMGB1 and VEGF messenger ribonucleic acid (mRNA) expression across leprosy groups and assessed their correlations. METHODS: This cross-sectional study included 146 participants: 35 with ENL, 36 with multibacillary leprosy without ENL, 38 with paucibacillary leprosy, and 37 healthy controls. HMGB1 and VEGF mRNA expression was measured by one-step SYBR Green quantitative reverse-transcription polymerase chain reaction. Group differences were analyzed by one-way analysis of variance with Tukey post hoc testing, correlations by Pearson's coefficient, and ENL versus multibacillary disease by multivariable linear regression adjusted for age, sex, bacterial index, and disease duration. RESULTS: HMGB1 expression differed across groups (13.530, 12.478, 9.585, and 9.442; F[3,142] =1579.960; P < 0.001; η 2 = 0.971), as did VEGF (10.992, 9.885, 8.341, and 8.277; F[3,142] =656.570; P < 0.001; η 2 = 0.933). ENL showed the highest expression; multibacillary leprosy without ENL was intermediate, and paucibacillary leprosy did not differ from controls. After adjustment, ENL remained associated with higher HMGB1 (B = 1.223; 95% confidence interval [CI]: 0.907-1.539) and VEGF expression (B = 1.327; 95% CI: 0.991-1.662); both P < 0.001. HMGB1 and VEGF were strongly correlated within all groups ( r = 0.980-0.989; all P < 0.001). CONCLUSIONS: ENL was associated with the highest HMGB1 and VEGF mRNA expression. Their strong co-variation does not establish a direct HMGB1-VEGF pathway or diagnostic validity.

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