Lymphocytes as Biomarkers of Therapeutic Response in Rheumatic Autoimmune Diseases, Is It a Realistic Goal?

Clin Rev Allergy Immunol. 2017 Oct;53(2):277-290. doi: 10.1007/s12016-017-8614-7.


Many therapies are available for patients with rheumatoid arthritis (RA) while biological therapies have limited effects in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). In both cases, biomarkers predicting drug response would be very useful to guide clinicians in their choice. We performed a systematic review to evaluate the value of lymphocyte phenotyping as a marker of therapeutic response. Of the 1063 articles retrieved, 39 fulfilled inclusion criteria and were included in the present review (25 for RA, 10 for SLE, and 4 for pSS). Lymphocyte phenotyping was described as a biomarker of therapeutic response in many studies, but most results could not be confirmed by independent teams using multivariate analysis. The most consistent result might be the association between rituximab response and the levels of memory B cells before therapy, although some studies were controversial. Thus, lymphocyte phenotyping cannot yet be proposed as a biomarker of response in rheumatic autoimmune diseases. The lack of reproducibility between studies may be explained by technical issues influencing lymphocyte phenotyping so standardization procedures should be developed for future studies. The patients' characteristics vary between studies, and large population studies, including a wide range of patients' characteristics and biomarkers, are required to provide predictive models for clinical outcomes. The use of new flow cytometry techniques such as single-cell mass cytometry technology might also help finder reliable biomarkers in the future.

Keywords: Autoimmune diseases; Biomarkers; Lymphocyte subsets; Personalized medicine; Predictive markers; Rheumatoid arthritis; Sjögren’s syndrome; Systemic lupus erythematosus; Therapeutic response.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / drug therapy*
  • Biomarkers, Pharmacological / metabolism*
  • Cell Separation
  • Flow Cytometry
  • Humans
  • Immunophenotyping / methods
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Prognosis
  • Reproducibility of Results
  • Rheumatic Diseases / diagnosis
  • Rheumatic Diseases / drug therapy*


  • Biomarkers, Pharmacological