Published online May 20, 2026.
https://doi.org/10.5021/ad.24.012
Clinical Importance of Autoantibodies to SOX10 and Lamin A/C as Potential Biomarkers in Sera From Vitiligo Patients
,1,*
Hyun Jeong Ju,2,*
Dong-Wha Yoo,1
Jung Min Bae,2
Sanghoon Lee,3
Seung-Chul Lee,4
and Ki-Ho Kim1
Abstract
Background
The discovery and evaluation of reliable biomarkers of vitiligo are important; however, no clinically established serological markers exist for predicting the clinical prognosis of vitiligo.
Objective
To investigate the levels of SOX10 and lamin A/C antibodies in the serum of patients diagnosed with vitiligo.
Methods
In this multicenter prospective study, blood serum samples were collected from adult vitiligo patients. The levels of SOX10 and lamin A/C antibodies were analyzed by direct sandwich enzyme-linked immunosorbent assay. Antibody levels between the groups were compared according to disease activity and subtype.
Results
A total of 80 patients (46 females; median age 60 years) were enrolled, including 56 (70%) with nonsegmental vitiligo and 27 (33.7%) with active disease. Positivity for SOX10 and lamin A/C antibodies was observed in 35.0% and 71.3% of patients, respectively. SOX10 positivity was significantly higher in active vitiligo than in stable vitiligo (59.3% vs. 24.5%; p=0.003), whereas lamin A/C positivity did not show significant difference (77.8% vs. 69.8%; p=0.60). No significant associations were found between SOX10 or lamin A/C status and the subtype, extent, or the presence of antinuclear antibody, anti-thyroid peroxidase, or anti-thyroglobulin (all p>0.05).
Conclusion
SOX10 antibody could be a potential marker for assessing disease activity in vitiligo. The increased production of SOX10 antibodies in the serum may be due to the underlying death or turnover of SOX10 containing cells under active autoimmune response.
INTRODUCTION
Vitiligo is a depigmented skin disease caused by the destruction of functional melanocytes (MCs) from the epidermis. Although multiple factors such as infections, stress, neural abnormalities, defective MC adhesion, and genetic susceptibility have been implicated in the development of vitiligo, the autoimmune hypothesis is a large part of vitiligo etiopathogenesis1, 2, 3, 4, 5.
The transcription factor SOX10 plays a crucial role in the normal development and differentiation of MCs and nerve cells from neural crest stem cells6. It has also been shown to promote the formation of large congenital nevi and melanomas7. Interestingly, elevated SOX10 levels were identified in vitiligo patients8, suggesting that greater immune-mediated lysis of MCs may be a significant indicator of vitiligo. Meanwhile, lamin A/C is a type V intermediate filament protein and a prominent component of nuclear lamina. Anti-lamin antibodies have been found in various autoimmune diseases9. Among the various subsets of MC autoantibodies found in the sera of vitiligo patients, non-specific antibodies, namely VIT 40/75/90, have been newly found in patients with vitiligo, which were eventually identified to be lamin A/C antibodies10. Minor insults from non-specific antibodies can cause lethal harm to MCs due to their vulnerability to immune-mediated injury, while surrounding cells remain unaffected11.
The role of SOX10 and lamin A/C antibodies as biomarkers of vitiligo in predicting the clinical course has not yet been demonstrated. Therefore, we aimed to evaluate the levels of SOX10 and lamin A/C antibodies in the sera of patients with vitiligo according to clinical subtype and disease activity.
MATERIALS AND METHODS
Study population
Patients with vitiligo (aged ≥19 years) were prospectively enrolled from November 2019 to May 2021 in Dong-A University Hospital (Busan), St. Vincent's Hospital, College of Medicine, The Catholic University of Korea (Suwon), Soonchunhyang University Bucheon Hospital (Bucheon), and Chonnam National University Hospital (Gwangju), South Korea. Patients who had received systemic treatment or phototherapy before the visit were excluded. Baseline data including disease onset, disease activity, clinical subtypes, involved anatomic areas, and positivity for additional autoantibodies, including antinuclear antibody (ANA), anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TGB), was collected. The subjects were categorized into four groups: clinical subtypes (segmental and nonsegmental) and disease activity (active or inactive). Active vitiligo was defined as the development of new lesions or enlargement of pre-existing lesions within the preceding 3 months, or relapse after repigmentation. This study was approved by the Institutional Review Board of The Catholic University of Korea in Suwon, South Korea (approval No. VC20TISI0021) Written informed consent was obtained from all study participants.
Sandwich enzyme-linked immunosorbent assay (ELISA) test
SOX10 and lamin A/C antibody expression levels were determined using the Sandwich ELISA. Capture antibodies specific for SOX10 antibody (Recombinant Anti-SOX10 antibody; Abcam, Cambridge, MA, USA) and lamin A/C antibody (Recombinant Anti-lamin A + lamin C antibody; Abcam) were coated onto the surface of a microtiter plate. The sandwich ELISA method uses highly specific antibodies to immobilize the target protein (antigen) to the plate and indirectly detect its presence. This method allows for the detection and quantification of target-specific proteins. The following section briefly describes the standard Sandwich ELISA, which uses a 96-well plate for colorimetric (chromogenic) detection. Six milliliters of blood were collected in SST tubes from the vitiligo patients, solidified for 1 day at 4°C or 60 minutes at room temperature, and centrifuged at 1,000 × g for 20 minutes. Patient sera were added to the plate to which the capture antibodies were applied. Secondary antibodies for both analytes were then applied, and they bound the remaining SOX-10 and lamin A/C. Then, a secondary antibody conjugate was added. This bound to the detection antibody and produced a detectable signal. SOX10 and lamin A/C antibody levels were considered positive at cut-off levels of >0.14 ng/ml and >0.057 ng/ml, respectively. Cut-off values for antibody positivity were defined using serum samples from healthy control individuals included in the reference dataset the company has provided. For established autoantibodies, positivity was determined based on clinically relevant thresholds: ANA was considered positive if any staining pattern other than “Negative” was observed, while anti-TPO and anti-TGB were defined as positive at levels >5.5 IU/ml and >6.0 IU/ml, respectively.
Statistical analysis
Descriptive variables are presented as mean and standard deviations for continuous variables and number (percentage) for categorical variables. Group comparisons of positivity rates for antibodies were performed across the following binary classifications: active vs. stable, segmental vs. nonsegmental, and localized vs. generalized. Categorical variables were compared using the Fisher’s exact test. Continuous variables were compared between groups using the Wilcoxon rank-sum test.
Statistical significance for the association between these categorical variables was assessed using Fisher’s exact test, which is appropriate for evaluating the independence of two binary variables in a clinical cohort. All statistical tests were two-sided, and p<0.05 was considered statistically significant. Analyses were conducted using available-case (complete-case) analysis for each comparison (i.e., participants with missing data for a given variable were excluded from that specific test).
RESULTS
Demographics of vitiligo patients
Eighty patients with vitiligo were enrolled; 46 females with a median age of 60 (range, 5–84). According to disease subtype and activity, 70% (56/80) had nonsegmental vitiligo, and 33.7% (27/80) had active vitiligo. The patients were categorized into four groups: active segmental group (n=12), active nonsegmental group (n=15), stable segmental group (n=12), and stable nonsegmental group (n=41). No significant difference was observed among groups in terms of age, sex, disease duration, and positivity for other autoantibodies (Table 1).
Table 1
Baseline demographics of included patients
SOX10 and lamin A/C antibody positivity in vitiligo and associated factors
Positivity for SOX10 and lamin A/C antibody was observed in 28/80 patients (35.0%) and 57/80 patients (71.3%), respectively. According to the disease activity, SOX10 positivity was significantly higher in active group (59.3%, 16/27) than in stable group (24.5%, 13/53; p=0.003), suggesting that SOX10 autoantibodies are associated with disease activity. In contrast, lamin A/C positivity did not show significant difference between active group (77.8%, 21/27) and stable group (69.8%, 37/53; p=0.60).
Regarding the vitiligo subtypes, SOX10 positivity was higher in the segmental group (50.0%, 12/24) than in the nonsegmental group (26.8%, 15/56), but this difference did not reach statistical significance (p=0.12). Lamin A/C positivity was 79.2% in segmental patients (19/24) and 66.1% in nonsegmental patients (37/56); the difference was not significant (p=0.58). No significant differences were observed for either SOX10 (36.4% vs. 32.1%; p=0.80) or lamin A/C (77.3% vs. 71.4%; p=0.59) between localized and generalized vitiligo (Fig. 1).
Fig. 1
Comparison of SOX10 and lamin A/C antibody values among groups.
Individual antibody levels for SOX10 and lamin A/C are presented as dot plots, categorized into four groups based on disease activity and distribution. The horizontal dashed red lines represent the cutoff values for positivity of each antibody.
SOX10 and lamin A/C antibody positivity in four-group analysis
SOX10 and lamin A/C positivity was the highest in the active segmental group (Table 2). SOX10 positivity varied considerably across the four groups (p=0.009). Lamin A/C ranged from 70.3% to 83.3% and did not differ significantly (p=0.85). Patients with active disease had higher SOX10 positivity; 66.7% (8/12) in the active segmental group and 53.3% (8/15) in the active nonsegmental group. In stable disease, SOX10 positivity dropped to 33.3% (4/12) in stable segmental and 17.1% (7/41) in stable nonsegmental groups. These results suggest that disease activity could drive SOX10 autoantibody production.
Table 2
Prevalence of SOX10 and lamin A/C antibodies in vitiligo patients according to activity and subtype
Association between positivity of SOX10 and lamin A/C antibodies and other autoantibodies
The analysis revealed no statistically significant correlation between the presence of SOX10 or lamin A/C antibodies and the positivity of ANA, anti-TPO, or anti-TGB (all p>0.05). The positivity rates of ANA, anti-TPO, and anti-TGB were similar regardless of SOX10 (41.4% vs. 39.2%; 48.3% vs. 47.1%; 27.6% vs. 27.5%) and lamin A/C status (40.4 vs. 39.1). Although the anti-TPO and anti-TGB positivity rates were numerically higher in the lamin A/C positive group compared to the negative group (52.6% vs. 34.8%; 29.8% vs. 21.7%), this difference did not reach statistical significance. These findings suggest that SOX10 and lamin A/C antibodies were expressed independently of conventional thyroid and nuclear autoantibodies in patients with vitiligo (Fig. 2).
Fig. 2
Relationship between SOX10 and lamin A/C Abs and other autoantibodies status. Bar graphs represent the percentage of patients testing positive for SOX10 and lamin A/C Abs, stratified by the positivity of ANA, anti-TPO, and anti-TGB.
ANA: antinuclear antibody, TPO: thyroid peroxidase, Ab: antibody, TGB: thyroglobulin.
DISCUSSION
The study demonstrated a significantly higher positivity rate of the SOX10 antibody in the active vitiligo group compared to the stable vitiligo group. A membrane antigen associated with vitiligo, lamin A/C antibody16, was increased in patients with vitiligo, but we could not find any correlation with disease subtype or activity.
Recent research has revealed several markers that drive the mechanisms of vitiligo, leading to the identification of potential biomarkers12. These circulating biomarkers included chemokines, soluble clusters of differentiation (CDs), and autoantibodies and have shown promising results. The levels of chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL10 showed a significant correlation with disease activity, and the level of CXCL9 was associated with treatment outcomes after autologous cultured MC transplantation13. Soluble CD25 was reported to be increased in active vitiligo compared to inactive patients14. Further studies on melanoma-associated vitiligo have shown that patients who responded well to immune checkpoint inhibitor immunotherapy had increased levels of both CXCL9 and CD2514. Several studies showed that S100B levels correlated with the course of vitiligo, which is increased in MCs during stress and released following death15. The positivity of anti-MC antibody was significantly increased during the disease progression phase, suggesting that the humoral mechanism has a role in the active phase of vitiligo16.
Meanwhile, the disease progression of melanoma, from tumor initiation and growth to the acquisition of invasive phenotypes, metastatic spread, and treatment resistance, has been linked with cellular differentiation and the hijacking of gene regulatory networks similar to the neural crest, the developmental structure that gives rise to MCs, and thus melanoma17. Blokzijl et al.8 observed that the serum levels of SOX10 were increased in both melanoma and vitiligo patients compared with healthy controls. Furthermore, it was found that individuals who responded to treatment had lower levels of serum SOX10. This suggests that SOX10 could be a valuable serum marker for monitoring treatment responses.
We suggest that the SOX10 antibody could be a potential serological marker for predicting vitiligo disease activity. The elevated levels of SOX10 in the serum may indicate an underlying destruction and/or increased turnover of SOX10-containing cells in vitiligo. Because SOX10 protein is known to regulate the development and function of MCs and neurons in terms of the specification of neural crest progenitors, vitiligo patients with high SOX10 expression could be expected to have more extensive and progressive disease18, 19.
Limitations of our study are a small sample size and a lack of healthy controls. In addition, no statistically significant difference in lamin A/C antibodies was noted between the groups; however, further studies will be necessary to evaluate the role of SOX10 and lamin A/C antibodies in the initial stage of vitiligo.
FUNDING SOURCE:None.
CONFLICTS OF INTEREST:The authors have nothing to disclose.
DATA SHARING STATEMENT:The de-identified individual participant data that support the findings of this study, as well as the study protocol and statistical analysis plan, are available from the corresponding author upon reasonable request. Data will be shared after publication and subject to approval of a brief proposal outlining the intended use.
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