Para-Phenylenediamine Sensitization and Polysensitization: TNF-α, CXCL11, and Immune-Regulatory Gene Polymorphisms

Background: Para-phenylenediamine (PPD) is a major hair dye allergen and often heralds broader contact allergy risk, yet the links among PPD sensitization, polysensitization (PS) and host genetics remain understudied. Objective: To quantify the association between PPD sensitization and PS in Korean patch test patients and to explore whether single nucleotide polymorphisms (SNPs) in selected immunoregulatory genes modulate this relationship. Methods: We retrospectively analysed 647 Korean patients patch tested with the Korean Standard Series. PS was defined as reactivity to ≥3 unrelated allergens; simultaneous positives to nickel, cobalt or chromate were counted as one event. Independent predictors of PPD sensitization were determined by multivariable logistic regression, and allergen networks were visualised with heatmaps. Seventeen patients were genotyped for SNPs in tumor necrosis factor-alpha, CXCL11, interleukin (IL)-10, IL-16 and STAT6. Results: PPD sensitization was confirmed in 38 patients (5.9%) and remained independently associated with PS (adjusted odds ratio [OR], 2.72; 95% confidence interval, 1.11-6.67). Additional chemical predictors were mercury ammonium chloride (OR, 3.68; p=0.018) and fragrance mix I (OR, 3.18; p=0.013). Heatmaps revealed dense preservative and rubber allergen clusters in PPD positive and particularly PS positive subsets. Exploratory genotyping showed numerical differences in CXCL11 variant frequency in PPD+/PS+ patients (85.7%) compared to expected population frequencies (about 50% in East Asians), though the small sample size (n=17) precluded statistical significance testing. Conclusion: PPD sensitization identifies patients at increased risk for PS and reactivity to mercury compounds and fragrance-related substances. Preliminary genetic observations require validation in larger studies to determine potential immunogenetic contributions.