A cluster of differentiation 19 + B-lymphocyte cell as a predictor of relapse in pemphigus vulgaris

Sir,

We read with keen interest the article “Identification of clinical and immunological factors associated with clinical relapse of pemphigus vulgaris in remission” published in the Indian Journal of Dermatology, Venereology and Leprology, issue 3, Volume 86.¹ The study methodology of using one-time assessment of cluster of differentiation 19+ B-lymphocyte cells and cluster of differentiation 19+ cluster of differentiation 27+ memory B cells’ count in an equal number of controls to have data regarding their counts in normal north Indian population does not seem to have enough external validity. Though a sample size of 40 for a rare disease like pemphigus seems acceptable, to derive the normal value of the cluster of differentiation 19+ B-lymphocyte cells in a population from 40 controls seems questionable given that the sample size is too small. Besides, the authors have not mentioned characteristics of controls in terms of age, sex, inclusion and exclusion criteria. A cluster of differentiation 19+ B-lymphocyte cell count can be confounded by many factors including immunogenetics of controls, recent infections and so on. Interestingly, data for normal values of various lymphocyte subpopulations in healthy Indians is available from a study conducted by a national task force constituted by the Indian Council of Medical Research.² Is there any specific reason for not using this data which was based on a much larger sample size and had the authors’ institute as one of the centers in the study?

A peripheral cluster of differentiation 19+ B-lymphocyte cell count is significantly influenced by steroid use and steroid withdrawal as reported in other conditions.³ Rituximab is the most potent cluster of differentiation 19+ B-lymphocyte depleter among all the previous treatments received by the patients in the study. Taking baseline cluster of differentiation 19+ B-lymphocyte cell count across the study population, which was treated with different treatment modalities in past with a few of them being on steroid and a few off steroid, add to the confounders in the final calculation of odds ratio. During a discussion of results, authors have compared their findings with that published by Albers et al., a study that was strictly limited to B cell repopulation after rituximab therapy.⁴ Correlation of disease relapse and repopulation of cluster of differentiation 19+ B-lymphocyte after B cell depletion therapies are well-studied now for pemphigus and other autoimmune disorders. Authors’ assumption that “B cell repopulation must occur irrespective of treatment modality used, preceding clinical relapse in a prototype immunoglobulin G-mediated disease,” seems too generalized considering that no other treatment like steroid, azathioprine or dexamethasone-cyclophosphamide pulse is known to deplete B-cell from circulation as thoroughly as rituximab.

Analysis of patients previously treated with rituximab vis-a-vis other treatment modalities and performing baseline cluster of differentiation 19+ B-lymphocyte cell count among them and exploring subsequent trends in both the groups would have thrown more light on this very interesting aspect of relapse in pemphigus vulgaris. Pilot study on a cluster of differentiation 19+ B-lymphocyte cell behavior with various treatment modalities may also help understand more about this immunological marker in pemphigus.