Session Information
Session Type: Abstract Submissions (ACR)
Title: The Associations of HLA-DRβ1 Shared Epitope Alleles and Serum Cytokines Among Postmenopausal Women with Rheumatoid Factor and Anti-Citrullinated Protein Antibody-Positive Rheumatoid Arthritis
Background/Purpose: This study evaluates associations between HLA-DRβ1 associated shared epitope (SE) alleles and cytokines among postmenopausal women with rheumatoid arthritis (RA). Presence of 1 or 2 versus absence of SE alleles is associated with more erosive RA in a number of studies. Fewer studies have examined if the number of SE alleles is associated with markers of inflammation.
Methods: Participants (n=2877) were enrolled in a substudy of the Women’s Health Initiative, and reported RA on questionnaires. Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), HLA- DRβ1 genotyping, and cytokines (IL-1B, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-12, IL-17, TNFα, MCP-1, MIF-1, IFN-Y, GCSF) were measured. SEs included QKRAA, KRRAA, RRRAA. Kruskal-Wallis tests were used to evaluate median cytokine concentrations by SE allele frequencies.
Results: Women included in this analysis (n=591) were RF and ACPA-positive. N=208 had 0 SE alleles, n=288 had 1 SE, and n=95 had 2 SEs. Several cytokines showed a dose-response increase from 0 to 1 to 2 SEs (underlined in table), with IL-2 and IL-6 showing the most marked differences (p<0.05 for differences between SE categories).
Table 1. Median (Interquartile Range) Cytokine Levels by Number of Shared Epitopes in ACPA/RF+ Women
|
|
Shared Epitopes |
|||
|
Cytokines |
0 (n=208) |
1 (n=288) |
2 (n=95) |
p-value
|
|
IL-2 |
11.3 (4.3-35.1) |
12.7 (5.6-41.6) |
19.0 (6.4-60.6) |
0.047 |
|
IL-6 |
11.8 (6.4-32.6) |
15.3 (8.5-35.3) |
20.3 (10.1-56.5) |
0.003 |
|
IFN-Y |
68.8 (39.1-171.2) |
77.4 (43.8-196.8) |
87.7 (48.6-214.6) |
0.22 |
|
MCP1 |
20.2 (13.4-33.1) |
21.5 (15.1-36.7) |
23.6 (13.5-42.6) |
0.24 |
|
IL-1b |
2.2 (1.4-5.0) |
2.4 (1.6-6.4) |
2.6 (1.7-7.1) |
0.18 |
|
IL-10 |
3.0 (2.0-5.3) |
3.2 (2.3-5.0) |
3.5 (2.4-5.7) |
0.32 |
|
IL-4 |
2.3 (1.3-3.7) |
2.32 (1.5-3.6) |
2.2 (1.5-3.2) |
0.80 |
|
IL-5 |
4.0 (2.8-5.9) |
4.2 (3.0-6.6) |
4.0 (2.9-6.0) |
0.46 |
|
IL-7 |
8.4 (6.0-11.5) |
8.6 (6.5-12.8) |
8.4 (6.1-11.6) |
0.47 |
|
IL-8 |
9.6 (7.4-12.8) |
10.1 (7.4-13.2) |
9.6 (7.3-12.7) |
0.50 |
|
IL-12 |
22.2 (12.2-65.5) |
23.3 (14.0-53.4) |
21.7 (13.5-69.6) |
0.82 |
|
IL-13 |
4.0 (2.3-10.5) |
4.4 (2.7-10.2) |
4.2 (2.6-11.3) |
0.46 |
|
GCSF |
165.8 (112.7-224.2) |
175.2 (120.0-235.8) |
167.4 (124.8) |
0.62 |
|
MIP1b |
44.2 (33.0-61.5) |
47.5 (34.4-65.8) |
45.9 (36.1-64.6) |
0.40 |
|
TNF-α |
35.3 (20.1-79.6) |
38.8 (23.6-88.5) |
38.5 (24.7-125.0) |
0.22 |
|
IL-17 |
4.6 (0-11.6) |
4.6 (0-13.3) |
3.1 (0-8.7) |
0.23 |
Conclusion: ACPA/RF+ women with 2 SE alleles had higher IL-2 and IL-6 levels than did women with fewer SE alleles. Studies indicate that Il-6 induces IL-2 proliferation, which in turn induces cytotoxic T cell differentiation. A pro-inflammatory milieu may explain why higher numbers of SE alleles are associated with more destructive arthropathy. IL-6 may be a particularly important therapeutic target among these women. Future work should examine whether these associations differ with use of disease-modifying anti-rheumatic drugs.
Disclosure:
M. Birru Talabi,
None;
R. Mackey,
None;
L. W. Moreland,
None;
J. Dorman,
None;
K. D. Deane,
None;
J. Sokolove,
None;
V. M. Holers,
None;
W. H. Robinson,
None;
B. Wallitt,
None;
L. Kuller,
None.
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-associations-of-hla-dr-shared-epitope-alleles-and-serum-cytokines-among-postmenopausal-women-with-rheumatoid-factor-and-anti-citrullinated-protein-antibody-positive-rheumatoid-arthritis/