Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine.

OBJECTIVE: People with autoimmune disease have worse COVID-19 infection-related outcomes, lower antibody responses to COVID-19 vaccine, and higher rates of breakthrough infection. Immunosuppressive medications used to treat rheumatoid arthritis (RA) are associated with lower COVID-19 vaccine responses, though independent contributions of comorbidities, T-cell immunity, and age are less clear. We sought to test the hypothesis that RA, immunosuppressive medications used to treat RA, and older age, contribute to reduced B and T cell response to COVID-19 vaccine. METHODS: We evaluated serum samples, taken the day of 1st vaccine dose, the day of 2nd dose, 2-6 weeks after 2nd dose, 7-12 weeks after 2nd dose, 13-24 weeks after 2nd dose, and 2-6 weeks after the 3rd dose, for anti-spike IgG and neutralizing antibody levels to Wuhan and Omicron BA.1 and peripheral blood mononuclear cells (PBMC) for spike-specific IFN-γ and IL-2 production by ELISPOT assay in 46 RA and 101 non-autoimmune control participants before and after the primary series COVID-19 mRNA vaccination. RESULTS: RA participants had lower spike-specific IgG and Wuhan-strain neutralizing antibody levels 2-6 weeks compared to controls after the second dose of primary vaccine series. Neutralizing antibody levels against Omicron BA.1 were low in both groups. IFN-γ production correlated with Wuhan neutralizing antibody levels, while older age negatively correlated with spike-specific IL-2, IFN-γ and IgG. Lower antibody levels were associated with older age, RA status, and medication usage, while lower T cell responses were associated primarily with older age. CONCLUSIONS: These data indicate lower COVID-19 mRNA vaccine-induced antibody levels in persons with RA compared to individuals without RA, likely partially attributable to immune suppressive medications. At the same time, older age is associated with lower antibody and cellular immune response to COVID-19 vaccines.

Reliability of C-reactive protein as an inflammatory marker in patients with immune-mediated inflammatory diseases and liver dysfunction.

Objectives: CRP is an acute-phase reactant widely used clinically as a marker of inflammation. CRP is a protein synthesized by hepatocytes. Previous studies have shown lower CRP levels in response to infections in patients with chronic liver disease. We hypothesized that CRP levels would also be lower during active immune-mediated inflammatory diseases (IMIDs) in patients with liver dysfunction. Methods: This retrospective cohort study used Slicer Dicer in Epic, our electronic medical record system, to search for patients with IMIDs both with and without concomitant liver disease. Patients with liver disease were excluded if there was no clear documentation of liver disease staging. Patients were also excluded if a CRP level was not available during disease flare or active disease. Arbitrarily, we considered normal CRP as ≤0.7 mg/dl, mild elevation of CRP as ≥0.8 and <3mg/dl, and elevated CRP as ≥3mg/dl. Results: We identified 68 patients with both liver disease and IMIDs (RA, PsA and PMR) and 296 patients with autoimmune disease and without liver disease. Presence of liver disease had the lowest odds ratio (odds ratio = 0.25, P < 0.0001) of having an elevated CRP during flare. Each specific IMID, except SLE and IBD, had higher median CRP levels during active disease episodes in patients without liver disease than in those with liver disease. Discussion: Overall, IMID patients with liver disease had lower serum CRP levels during active disease than their counterparts without liver dysfunction. This observation has implications for clinical use of CRP level as a reliable marker of disease activity in patients with IMIDs and liver dysfunction.

Association of hidradenitis suppurativa with autoimmune disease and autoantibodies.

Objective: There is thought to be an association between hidradenitis suppurativa (HS) and autoimmune diseases. This retrospective longitudinal cohort study looked to identify whether certain autoimmune diseases or autoantibody specificities are more closely associated with HS than others and whether such associations are related to the severity of HS. Methods: Patients were identified using the SlicerDicer search tool in Epic from 1 January 2010 to 15 August 2020. Search criteria included HS diagnosis by ICD-10 code (L73.2) and at least one visit to the dermatology department. Charts were reviewed to determine HS disease severity, treatment modalities, presence of autoimmune disease and autoantibody positivity. Results: Six hundred and twenty-seven patients were identified. Most patients were female (75.3%) and had obese BMIs (71.1%), but there were no significant demographic differences between HS patients with and without autoimmune diseases. One hundred and one (16.1%) patients in the total cohort had at least one autoimmune disease, most commonly thyroid disease, lupus, psoriasis and IBD. Two hundred and twelve patients were also tested for the presence of autoantibodies. The most common positive autoantibody, found in 54 patients (28.4%), was ANA. Fifty-four patients with more severe HS disease manifestations required biologic medications to treat their HS. Neither HS severity nor biologic treatment was associated with presence of autoimmune disease or positive autoantibodies. Conclusion: In a large cohort of patients with HS followed longitudinally, autoimmune disorders (especially lupus, psoriasis and IBD) and presence of autoantibodies were more commonly observed than expected in the normal population.

Use of upadacitinib in the treatment of psoriatic arthritis.

Upadacitinib, a selective JAK1 inhibitor, has been evaluated for efficacy and safety in the treatment of psoriatic arthritis (PsA). Relevant literature using the terms 'upadacitinib' and 'PsA' were identified via PubMed and Google Scholar. Efficacy of upadacitinib in the treatment of PsA versus placebo was demonstrated in the SELECT-PsA I and II trials. SELECT-PsA1 also showed upadacitinib was noninferior to adalimumab in the treatment of PsA. The most common adverse events in patients treated with upadacitinib were infections, malignancies and thromboembolic events. Upadacitinib is an effective medication that can be used in the treatment of active PsA. Despite its proven efficacy and safety, upadacitinib does not yet have long-term safety data.

PL-7 Antisynthetase Syndrome in Association with Sjögren's, Systemic Lupus Erythematosus, and Rheumatoid Arthritis.

We present a rare case of PL-7 antisynthetase syndrome (ASS) in association with Sjögren's, systemic lupus erythematosus (SLE), and seropositive rheumatoid arthritis (RA). Initially, the patient was diagnosed with Sjögren's followed by Sjögren's/SLE overlap and then Sjögren's/SLE/RA overlap. She was eventually diagnosed with Sjögren's/SLE/RA overlap with PL-7 ASS with interstitial lung disease (ILD). ILD was discovered after complaints of pleuritic chest pain with subsequent workup with coronary computed tomography (CT) revealing pulmonary fibrosis. This case demonstrates the ambiguity with which symptoms of ASS can present; given the high respiratory morbidity and mortality of ASS especially in non-Jo-1 patients, those who present with Raynaud's, myositis, or joint pain, whether together or in isolation, should be assessed for presence of additional features of ASS and potentially undergo testing for ASS antibodies if appropriate.

Treatment of advanced stage methotrexate-associated lymphoproliferative disorders (MTX-LPDs) with methotrexate discontinuation.

We present two cases of patient's with long-standing autoimmune diseases being treated with immunosuppressants that developed aggressive lymphoproliferative disorders. Immunosuppressants have a well-known association with disorders. Sustained regression of these lymphoproliferative disorders occurred with simple discontinuation of these immunosuppressive agents.