Sir,Pemphigus is a rare, chronic, and potentially life-threatening autoimmune bullous disease, characterized by widespread blistering and erosions of skin and mucous membranes in which autoantibodies are directed against desmosomal glycoproteins (desmoglein1-Dsg1 and desmoglein3-Dsg3) resulting in the loss of keratinocyte cell–cell adhesion.[1] Autoantibodies against Dsg1 and Dsg3 show a significant association with types of pemphigus, likewise presence of anti-Dsg3 in mucosal dominant type of pemphigus vulgaris (PV), anti-Dsg1 in cutaneous dominant type of pemphigus foliaceus (PF), and anti-Dsg1 and anti-Dsg3 in mucocutaneous type of PV and PF. The purpose of this study was to evaluate the possible immunodiagnostic significance of anti-Dsg1 and anti-Dsg3 autoantibodies detected by ELISA in pemphigus patients from western India and to correlate them with disease severity.In this prospective study, newly diagnosed biopsy-proven pemphigus patients (n = 150) aging 18 years and above were enrolled during the period of July 2017 to October 2018. This study was approved by Institutional Ethics Committee of National Institute of Immunohaematology (ICMR-NIIH) and patients were enrolled after obtaining written informed consent. Patients with drug-induced morbidities, other autoimmune blistering disease overlaps, and relapse episodes or complete remission were excluded from study. Clinical history, skin or mucosal histopathological findings (n = 150), and direct immunofluorescence (DIF; n = 70) findings were recorded. Disease severity for mucosal and cutaneous involvement was assessed using Mahajan disease severity score.[2] Serum anti-Dsg1 and anti-Dsg3 antibodies levels were detected using commercially available semiquantitative ELISA kits (EUROIMMUN, Lübeck, GERMANY) where an index value higher than equal to 20.0 RU/ml was considered positive. Statistical analyses were performed using GraphPad Prism Version 6.0 (GraphPad Software, La Jolla, CA, U.S.A.), where data was considered statistically significant at P < 0.05.In our study, we report a high prevalence of PV patients (80%) in comparison to PF patients (20%). High female preponderance was observed in PV patients, while in PF patients, male population was found to be highly prevailing. The mean age at evaluation was observed to be 46.9 ± 13.2 and 52.3 ± 15.1 years in PV and PF patients, respectively. Demographic and phenotypic details are summarized in Table 1.
Table 1
Demographic details of pemphigus patients studied (n=150)
Demographic features
PV (%)
PF (%)
Patients (n=150)
120 (80)
30 (20)
M: F
0.5:1
1.5:1
Age at evaluation in years
46.9±13.2
52.3±15.1
<40 years
33 (27.5)
6 (20)
40-60 years
71 (59.2)
13 (43.3)
>60 years
16 (13.3)
11 (36.7)
Clinical manifestations
Cutaneous
1 (0.8)
24 (80)
Oral
38 (31.7)
0 (0)
Mucocutaneous
81 (67.5)
6 (20)
Demographic details of pemphigus patients studied (n=150)PV patients showed 100% and 75% positivity for anti-Dsg3 and anti-Dsg1 autoantibodies, respectively. In PF group, all patients (n = 30) were positive for anti-Dsg1 autoantibody, whereas 11 patients (37%) were positive for anti-Dsg3 autoantibody. Percentage positivity for anti-Dsg1 and anti-Dsg3 autoantibodies was higher among pemphigus patients with age group ranging between 40 and 60 years. PV patients with mucocutaneous manifestations had significantly elevated levels of anti-Dsg1 and anti-Dsg3 autoantibodies (P < 0.05). Anti-Dsg3 autoantibody levels were significantly elevated in PF patients with mucocutaneous involvement as compared to those with cutaneous involvement (P < 0.05).Anti-Dsg1 and anti-Dsg3 autoantibody levels in PV patients positively correlated with mucosal and cutaneous involvement (P < 0.05). In PF patients, anti-Dsg3 levels positively correlated with mucosal involvement (r = 0.6790; P = < 0.0001). Statistically significant elevated anti-Dsg1 and anti-Dsg3 autoantibody levels were observed in PV patients having severe or extensive mucosal and cutaneous disease severity (P < 0.05). In PF patients, anti-Dsg3 autoantibody levels were significantly elevated in patients having moderate mucosal disease severity (P < 0.05).Among 70 pemphigus patients, 57 PV patients (98.2%) and 11 PF (92.3%) patients showed positivity for IgG and C3 depositions on DIF. It was noted that DIF positivity in PV and PF patients was statistically significantly associated with anti-Dsg1 and anti-Dsg3 autoantibodies, respectively (P < 0.0001). Interestingly one male from each PV and PF group showed negative DIF findings and positive histopathology and ELISA findings. Clinically these two males showed severe disease severity scores and elevated levels for anti-Dsg1 and anti-Dsg3 autoantibodies.Our findings are in concordance with studies worldwide except for South America and Africa where the prevalence of PF is higher to PV.[3] Studies from different parts of India have reported findings similar to our study.[45] Detection of anti-Dsg1 and anti-Dsg3 autoantibody levels by ELISA can serve as a good serological diagnostic tool for assessing the disease severity. Further studies in pemphigus patients and their sequential follow-up are required to understand the epitope shift phenomenon and the underlying mechanism involving in the transition of PV into PF and vice versa for usefulness of ELISA to test these autoantibodies for their prognostic utility.
Declaration of patient consent
The authors certify that the consent forms have been obtained during enrolment.
Financial support and sponsorship
This work was supported by the intramural fund by Indian Council of Medical Research-National Institute of Immunohaematology (ICMR-NIIH).