Assessment of CXCL10 and S100B serum levels in patients with vitiligo before and after narrow-band ultraviolet B therapy: A quasi-experimental study

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Vitiligo is characterised by the elevated expression of melanocyte-specific cytotoxic T-cells, leading to melanocyte death. The CXC-chemokine Ligand 10 (CXCL10) enhances chemoattraction and epidermal localisation of cytotoxic T-cells.¹ S100B is a calcium binding protein expressed in melanocytes and released extracellularly upon their death.² UVB narrow-band therapy (NB-UVB) is an effective vitiligo treatment that inhibits cytotoxic T-cells and promotes melanocyte migration.³ The need for serological marker changes to identify the possibility of re-pigmentation during NB-UVB therapy is crucial. Moreover, targeting these molecules will be a significant advancement in vitiligo treatment. This study aimed to evaluate CXCL10 and S100B serum levels in vitiligo patients before and after NB-UVB therapy compared to controls.

This quasi-experimental study included 20 patients with non-segmental vitiligo. Patients with autoimmune disorders, infections, light sensitive disorders, malignancy, systemic vitiligo treatment within the last three months were excluded. Vitiligo severity was assessed using Vitiligo Extent Score (VES).^S1 Vitiligo activity was assessed via Vitiligo Disease Activity (VIDA) score^S2 and evaluating vitiligo activity signs^S3 (ill-defined borders, leukotrichia, recent koebnerization, and confetti depigmentation). In addition, twenty controls without a history of vitiligo, autoimmune diseases or cancers were recruited.

The study was performed following the Helsinki Declaration principles and was approved by the Institutional Research Ethics committee. All participants signed a written informed consent form.

Phototherapy was administered for 24 sessions, three times a week on non-consecutive days, in a phototherapy unit equipped with 16 fluorescent tubes (peak emission wavelength 311-312 nm) (TL-100W/01, Philips & Eindhoven). Patients’ lesional skin was considered Fitzpatrick skin phototype I, with a minimal erythema dose (MED) of 400 mJ/cm². The starting fluence was 70% of MED (280 mJ/cm²), with 15% increase in each session. If severe erythema, burning pain, or blistering occurred, sessions were stopped until erythema subsided to a pale pink, then resumed at the final tolerated dose. ^S4 Patients were examined every 2 weeks for re-pigmentation. Two weeks after the 24^th session, VES and activity signs were reassessed.

A 5 mL venous blood sample was collected in plain test tubes from each participant, left at room temperature for 20 minutes, then centrifuged for 10 minutes at 4000 rpm. The separated serum was kept at -20°C till needed. CXCL10 and S100B serum levels were measured pretreatment and two weeks after the 24^th session using an enzyme linked immune-sorbent assay [Supplementary File 1] as recommended by the manufacturers.

Vitiligo patients were 15 (75%) females and 5 (25%) males, ranging in age from 18-59 years (mean 28.75±11.60 years). Healthy controls were 14 (70%) females and 6 (30%) males, ranging in age from 19-58 years (mean 31.60±11.71 years). There were no significant differences in age or sex between patients and controls. Table 1 summarises the patients’ clinical data.

Post-treatment, re-pigmentation was detected in 17 (85%) patients [Figure 1a and b], VES was significantly reduced (p=0.028), as were the clinical activity signs (p=0.016). None of the patients showed new lesions of koebnerization, or ill- defined borders and half of patients with leukotrichia didn’t show any new white hairs [Supplementary Table 1].

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Figure 1a:

A 22-year-old woman patient presented with vitiligo lesions in the back of neck, chest, and left leg (left side). Right panel showing marginal and follicular re-pigmentation after 24 sessions of NB-UVB therapy.

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Figure 1b:

A 24-year-old woman presented with generalized vitiligo (left panel). Right thigh and leg lesions showing marginal and follicular re-pigmentation after 24 sessions of NB-UVB therapy.

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In vitiligo patients, the pretreatment levels of both CXCL10 (mean 11.40±5.89, median 9.05, range 3.90-22.10 pg/mL) and S100B (mean 40.91±12.76, median 38.38, range 31.30-93.30 pg/mL,) were significantly higher than the post-treatment levels (CXCL10 levels: mean 6.34±4.54, median 4.8, range 3.20-21.55 pg/mL; S100B levels: mean 37.92±11.67, median 34.98, range 29.50-83.60 pg/mL) (p=0.004, p=0.02). The baseline pre-treatment levels of CXCL10 and S100B in vitiligo patients were also significantly higher than their levels in healthy controls (CXCL10 levels: mean 7.62±5.18, median 6.9, range 1.10-19.74 pg/mL; S100B levels: mean 33.72±2.74, median 33.5, range 30.0-38.50 pg/mL) (p=0.021, p<0.001). There were no significant differences between post-treatment levels and healthy controls’ levels [Figure 2a and b]. Significant positive correlations were found between VIDA score and both CXCL10, and S100B pretreatment levels (p<0.001, p=0.02) [Supplementary Figure 1].

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Figure 2a:

Serum CXCL10 level in patients with vitiligo (n=20) before and after NB-UVB compared to healthy controls (n=20).

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Figure 2b:

Serum S100B level in patients with vitiligo (n=20) before and after NB-UVB compared to healthy control (n=20). SD: Standard deviation. Wilcoxon signed ranks test (p1) was used for comparing between serum levels of markers before and after NB-UVB therapy. Mann Whitney test was used for comparing between pretreatment levels and levels in healthy controls (p2), as well as post-treatment levels and levels in healthy control (p3). *: Statistically significant at p < 0.05.

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Similar to these findings, several studies reported higher CXCL10^1,4 and S100B^{2, 5} levels in vitiligo patients compared to controls, with a significant correlation with disease activity. CXCL10, and S100B may thus be markers for vitiligo activity. Furthermore, prior studies detected significant reduction in CXCL10 expression in vitiligo patients after NB-UVB therapy.^{6, 7}

There was no significant association between post-NB-UVB re-pigmentation and patients’ clinical data or pretreatment levels of both markers [Supplementary Tables 2 and 3], implying that baseline levels of these markers didn’t correlate with the possibility of re-pigmentation after NB-UVB therapy

Only patients with post-NB-UVB re-pigmentation had significantly lower post-treatment CXCL10 and S100B levels than at baseline (p=0.001, p=0.011) [Supplementary Table 2]. This significant reduction in CXCL10 and S100B levels during NB-UVB therapy may therefore be indicative of re-pigmentation. To our knowledge, this is the first study to investigate the changes in S100B levels after NB-UVB therapy.