Soluble HLA‐DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease‐associated epitopes

Abstract

We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.

Soluble HLA-G in Rheumatoid Arthritis

“…This may be partly due to the low disease activity in many patients, a variety of treatments, and parameters such as joint pain, HAQ, and VAS for pain may be influenced by accumulation of lesions and not only by present disease activity. We have previously shown a correlation between soluble HLA-DR and several of these parameters of disease activity [26]. However, in the present patients comparison of soluble HLA-G in groups with different therapies did not provide evidence that the therapy may have a determining role in the present conclusions (data not shown).…”

“…Soluble HLA-G levels were relatively high in the presence of disease-associated epitopes and correlated significantly with several parameters of disease activity or severity: EULAR joint swelling score, CRP, and RF by latex fixation and Waaler-Rose test [26,32]. However, we found no significant correlation with ESR, EULAR joint pain score, HAQ, and VAS for pain (Table 1).…”

“…Disease susceptibility and severity in RA are partially linked to "disease-associated epitopes," i.e., sequences of amino acids in the third hypervariable region of the HLA-DRB1-encoded chain (mainly DRB1*01, 04, and 10) [22][23][24][25][26]. In this study, we investigated plasma soluble HLA-G and soluble HLA-I levels in patients with RA and their potential relationships with disease activity and with the presence of shared epitopes and certain HLA-DRB1* and HLA-DQB1* alleles.…”

Hyperosmolar Stress Upregulates HLA-DR Expression in Human Conjunctival Epithelium in Dry Eye Patients and In Vitro Models

“…In our experiment, high HLA-DR expression was found to be associated with an elevated subjective symptoms score, in agreement with findings in rheumatoid arthritis, in which a relationship between serum HLA-DR concentration and pain score has been demonstrated, and the role of proinflammatory cytokines in pain development hypothesized. 40 However, no statistically significant correlation coefficients between each of these three parameters (conjunctival inflammatory score, ocular surface metaplasia, and subjective symptoms score) and HLA-DR expression have been found, perhaps due to a certain degree of biological variability in expression of the antigen itself.…”

T Cells Survey the Stability of the Self: A Testable Hypothesis on the Homeostatic Role of TCR-MHC Interactions

“…This is based on a calculation using the law of mass action (where we assumed that in a human in 5 litres of blood there are ∼5 × 10 9 T cells, each of which bears about 30,000 antigen-receptor molecules on its surface, the concentration of the s-pMHCs is of the order of 142 ± 13 ng/ml [73] and the affinity of the s-TCR is ∼10 5 M –1 [74]).…”