Brief Report: Altered Innate Lymphoid Cell Subsets in Human Lymph Node Biopsy Specimens Obtained During the At-Risk and Earliest Phases of Rheumatoid Arthritis

Arthritis Rheumatol. 2017 Jan;69(1):70-76. doi: 10.1002/art.39811.


Objective: Innate lymphoid cells (ILCs) are emerging mediators of immunity, and accumulation of inflammatory ILC populations can occur in inflammatory-mediated conditions. Since early lymph node (LN) activation has been shown in rheumatoid arthritis (RA), we aimed to investigate the frequency and distribution of ILCs in LN biopsy specimens obtained during the earliest phases of RA.

Methods: Twelve patients with early RA, 12 individuals with IgM rheumatoid factor and/or anti-citrullinated protein antibodies without arthritis (RA risk group), and 7 healthy controls underwent ultrasound-guided inguinal LN biopsy. ILC subsets and the expression of vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) by LN endothelial cells and fibroblasts were analyzed by flow cytometry.

Results: Although no differences in the frequencies of total ILCs (Lin-CD45+/low CD127+) were found, the distribution of the ILC subpopulations differed among groups. RA patients showed lower numbers of lymphoid tissue-inducer (LTi) cells (c-Kit+NKp44- ILCs) and increased ILC1 (c-Kit-NKp44- ILCs) and ILC3 (c-Kit+NKp44+ ILCs) numbers compared with controls (P < 0.001, P < 0.050, and P < 0.050, respectively). Individuals at risk of RA exhibited an increased frequency of ILC1 compared with controls (P < 0.01). LTi cells paralleled the expression of adhesion molecules on endothelial cells and fibroblasts.

Conclusion: Our findings indicate that during the at-risk and earliest phases of RA, the ILC distribution in LN changes from a homeostatic profile toward a more inflammatory profile, thereby providing evidence of a role for ILCs in RA pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / pathology*
  • Biopsy
  • Female
  • Humans
  • Lymph Nodes / pathology*
  • Lymphocytes*
  • Male
  • Middle Aged
  • Risk Factors
  • Severity of Illness Index