Search

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/., The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

Background:Pain is a common, difficult to manage symptom in hand osteoarthritis (OA). Multiple pain mechanisms may play a role in hand OA.Objectives:To investigate presence of neuropathic pain symptoms in patients with inflammatory hand OA, characteristics of those patients, their impact on health related quality of life (HR-QoL), and the influence of anti-inflammatory treatment on neuropathic pain symptoms.Methods:Data from a randomised, double-blind, placebo-controlled trial of prednisolone including 92 patients with hand OA fulfilling ACR criteria were used. At baseline patients had signs of synovial inflammation, a VAS finger pain of ≥30 mm and who flared ≥20 mm upon NSAID washout. The primary endpoint was VAS finger pain (0-100) at week 6.Neuropathic pain symptoms were measured at baseline and week 6 using the validated painDETECT questionnaire, consisting of questions on pain quality, pain intensity over time and radiating pain. Scores range -1 to 38 and patients are classified as having unlikely (18) neuropathic pain. HR-QoL was measured with physical component scale (PCS) of Short-Form 36 (SF36; 0-100), comorbidities with the Self-administered Comorbidities Questionnaire (SCQ; 0-45), radiographic severity with Kellgren-Lawrence (KL) sum score (0-120), and treatment response with OMERACT-OARSI responder criteria.Association of patient characteristics with neuropathic pain symptoms was analysed with univariate and multivariate ordinal logistic regression, with painDETECT as dependent variable. Association of neuropathic pain symptoms with HR-QoL was analysed with multivariate linear regression, adjusted for age, sex, BMI, VAS finger pain, SCQ score and KL sum score, with PCS as dependent variable. Response of neuropathic pain symptoms and VAS pain to prednisolone was analysed with generalised estimating equations. Association of neuropathic pain symptoms at baseline with response to treatment was analysed using χ2-tests and GEE.Results:91 patients had complete painDETECT data at baseline (mean painDETECT score 12.8 [SD 5.9]). Scores were 18 in 16%. Higher painDETECT score categories were associated with less radiographic damage, more comorbidities, female sex and higher VAS finger pain in multivariate analysis. (table 1)Table 1.Ordinal logistic regression with painDETECT categories as dependent variableVariablesMean (SD) N=91 (100%)Odds ratio (95% CI)Age64 (9)0.96 (0.90 to 1.02)Female sex; N (%)72 (79%)3.84 (1.19 to 12.39)*BMI; median (SD)27 (24 to 29)0.97 (0.89 to 1.06)SCQ score; median (SD)2 (1 to 5)1.04 (1.04 to 1.36)*VAS finger pain53.8 (2.1)1.02 (1.00 to 1.04)*KL sum score37 (16)0.96 (0.93 to 1.00)**pPatients with painDETECT scores >18 had a lower HR-QoL (PCS -6.5 [95%CI -10.4 to -2.6]) than those with painDETECT scores PainDETECT scores remained unchanged throughout the trial in both prednisolone-treated and placebo-treated patients, and there was no between-group difference at week 6. VAS pain improved more in the prednisolone group than in the placebo group (mean between-group difference -16.5 [95%CI -26.1 to -6.9]) (figure 1). No association between the presence of neuropathic pain symptoms at baseline and OMERACT-OARSI response to treatment was found.Conclusion:Patients with inflammatory hand OA and additional neuropathic pain symptoms are more often female and have more comorbidities, and report a lower QoL, than those without. Neuropathic pain symptoms seem unresponsive to anti-inflammatory therapy. Clinicians should be aware of neuropathic pain symptoms in their patients as they might benefit from additional, specific treatment.Acknowledgements:The authors thank all patients for their participation in the HOPE study, and participating rheumatologists for inclusion of patients in the HOPE study. We also thank research nurses B.A.M.J. van Schie-Geyer and S. Wongsodihardjo, and technicians J.C. Kwekkeboom and E.I.H. van der Voort, for their contributions.Disclosure of Interests:Coen van der Meulen: None declared, Lotte van de Stadt: None declared, Féline Kroon: None declared, Marion Kortekaas: None declared, Annelies Boonen Speakers bureau: Lecture for UCB; paid to department., Consultant of: Yes. Advisory board meetings at Galapagos, Eli Lilly and Abvvie; paid to department., Grant/research support from: Yes. Grants by Celgene and Abbvie; paid to department., Stefan Böhringer: None declared, Marieke Niesters: None declared, Monique Reijnierse: None declared, Frits Rosendaal: None declared, Naghmeh Riyazi: None declared, M. Starmans: None declared, Franktien Turkstra: None declared, Jende van Zeben: None declared, Cornelia Allaart: None declared, Margreet Kloppenburg Consultant of: For Abbvie, Pfizer, Levicept, GlaxoSmithKline, Merck-Serono, Kiniksa, Flexìon, Galapagos, Jansen, CHDR and local investigator of industry-driven trial (Abbvie). All fees were paid to the institution., Grant/research support from: Grant by the Dutch Arthritis Society