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The paradox of high availability and low recognition of soluble HLA-G by LILRB1 receptor in rheumatoid arthritis patients.

Veit TD, Chies JA, Switala M, Wagner B, Horn PA, Busatto M, Brenol CV, Tavares Brenol JC, Machado Xavier R, Rebmann V - PLoS ONE (2015)

Bottom Line: Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027).Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033).Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14 pb genotype.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
HLA-G is a regulatory molecule involved in immunologic tolerance. Growing evidence indicates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. This study aimed at a systematic evaluation of soluble HLA-G (sHLA-G) in plasma of rheumatoid arthritis (RA) patients with long-lasting chronic inflammation. RA patients (n=68) and healthy controls (n=26) had their plasmatic sHLA-G measured by ELISA whereas the binding capability of sHLA-G to its cognate LILRB1 receptor was measured by a Luminex-based assay. All subjects were PCR-genotyped for HLA-G 14 bp polymorphism (rs66554220). Significantly higher sHLA-G levels were observed in patients (p<0.001), however no significant differences were observed in LILRB1 binding capacity between RA patients and controls. Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027). Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033). Furthermore, methotrexate treated patients (n=58) revealed significantly lower LILRB1 binding to sHLA-G molecules than non-treated patients (medians: 12.2 vs. 67.7 units/ml, p=0.031). Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14 pb genotype. Thus, in a substantial number of late RA patients, the circulating sHLA-G molecules are impaired regarding LILRB1 recognition, meaning that although increased levels are observed; these molecules are not qualified to exert their protective functions against inflammation. Our findings offer new insights into the immunopathology of RA patients with long-lasting anti-RA-treatment and highlight the importance to also measure the binding capability of sHLA-G to LILRB1.

No MeSH data available.


Related in: MedlinePlus

Soluble HLA-G level in plasma and its recognition by LILRB1 in RA patients and healthy controls.RA = Rheumatoid arthritis
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pone.0123838.g002: Soluble HLA-G level in plasma and its recognition by LILRB1 in RA patients and healthy controls.RA = Rheumatoid arthritis

Mentions: In order to investigate whether sHLA-G levels were altered in the periphery among late rheumatoid arthritis patients, we analyzed sHLA-G in plasma samples in 68 RA patients with mean disease duration of about 12 years (Table 1). The sHLA-G plasma levels were significantly increased in RA patients as compared to healthy controls (p<0.001, Mann-Whitney test, Fig 2): The median sHLA-G level of RA patients was 9.3 ng/ml (range: 0–131.9 ng/ml) and in healthy individuals 4.6 ng/ml (range: 0–20.4 ng/ml). Of note, 18 patients (26.5%) exhibited sHLA-G levels above the controls’ highest concentration (Fig 2). With respect to sHLA-G levels and disease activity parameters, however, no significant correlations were observed (Table A in S1 File). In addition, no significant correlations could be observed between sHLA-G levels and anti-RA treatment regimen (Table B in S1 File).


The paradox of high availability and low recognition of soluble HLA-G by LILRB1 receptor in rheumatoid arthritis patients.

Veit TD, Chies JA, Switala M, Wagner B, Horn PA, Busatto M, Brenol CV, Tavares Brenol JC, Machado Xavier R, Rebmann V - PLoS ONE (2015)

Soluble HLA-G level in plasma and its recognition by LILRB1 in RA patients and healthy controls.RA = Rheumatoid arthritis
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390237&req=5

pone.0123838.g002: Soluble HLA-G level in plasma and its recognition by LILRB1 in RA patients and healthy controls.RA = Rheumatoid arthritis
Mentions: In order to investigate whether sHLA-G levels were altered in the periphery among late rheumatoid arthritis patients, we analyzed sHLA-G in plasma samples in 68 RA patients with mean disease duration of about 12 years (Table 1). The sHLA-G plasma levels were significantly increased in RA patients as compared to healthy controls (p<0.001, Mann-Whitney test, Fig 2): The median sHLA-G level of RA patients was 9.3 ng/ml (range: 0–131.9 ng/ml) and in healthy individuals 4.6 ng/ml (range: 0–20.4 ng/ml). Of note, 18 patients (26.5%) exhibited sHLA-G levels above the controls’ highest concentration (Fig 2). With respect to sHLA-G levels and disease activity parameters, however, no significant correlations were observed (Table A in S1 File). In addition, no significant correlations could be observed between sHLA-G levels and anti-RA treatment regimen (Table B in S1 File).

Bottom Line: Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027).Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033).Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14 pb genotype.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunogenética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

ABSTRACT
HLA-G is a regulatory molecule involved in immunologic tolerance. Growing evidence indicates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. This study aimed at a systematic evaluation of soluble HLA-G (sHLA-G) in plasma of rheumatoid arthritis (RA) patients with long-lasting chronic inflammation. RA patients (n=68) and healthy controls (n=26) had their plasmatic sHLA-G measured by ELISA whereas the binding capability of sHLA-G to its cognate LILRB1 receptor was measured by a Luminex-based assay. All subjects were PCR-genotyped for HLA-G 14 bp polymorphism (rs66554220). Significantly higher sHLA-G levels were observed in patients (p<0.001), however no significant differences were observed in LILRB1 binding capacity between RA patients and controls. Remarkably, the proportion of patients presenting specific binding of sHLA-G to LILRB1 was significantly decreased as compared to controls (56% vs. 81%, p=0.027). Patients without rheumatoid factor (RF-) were significantly overrepresented in the group of patients positive for LILRB1 binding as compared to patients without LILRB1 binding (31% vs 10%, p=0.033). Furthermore, methotrexate treated patients (n=58) revealed significantly lower LILRB1 binding to sHLA-G molecules than non-treated patients (medians: 12.2 vs. 67.7 units/ml, p=0.031). Unlike in controls, no significant differences in sHLA-G levels were observed among patients grouped by 14 pb genotype. Thus, in a substantial number of late RA patients, the circulating sHLA-G molecules are impaired regarding LILRB1 recognition, meaning that although increased levels are observed; these molecules are not qualified to exert their protective functions against inflammation. Our findings offer new insights into the immunopathology of RA patients with long-lasting anti-RA-treatment and highlight the importance to also measure the binding capability of sHLA-G to LILRB1.

No MeSH data available.


Related in: MedlinePlus