Clinical Reviews in Allergy & Immunology

, Volume 53, Issue 2, pp 277–290 | Cite as

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

  • Kristina Schreiber
  • Gaetane Nocturne
  • Divi Cornec
  • Claire I. Daïen


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.


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



Thanks are due to Sumaiya Hoque for editing the English language.

Compliance with Ethical Standards

Conflicts of Interest

CID has received honoraria from BMS, MSD, Pfizer, Roche-Chugai, and UCB and research grants from MSD, Pfizer, Roche-Chugai, and UCB.


No funding was received.

Ethical Approval and Informed Consent

This article is a review of studies that fulfilled the ethical standards.

Supplementary material

12016_2017_8614_MOESM1_ESM.docx (59 kb)
Supplementary Table 1 (DOCX 58 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Kristina Schreiber
    • 1
  • Gaetane Nocturne
    • 2
  • Divi Cornec
    • 3
  • Claire I. Daïen
    • 1
    • 4
  1. 1.Rheumatology DepartmentLapeyronie Hospital and Montpellier I UniversityMontpellierFrance
  2. 2.Rheumatology DepartmentParisFrance
  3. 3.Rheumatology DepartmentBrestFrance
  4. 4.Institute of Molecular GeneticUMR 5535, CNRSMontpellierFrance

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