Cytomegalovirus colitis unmasking human immunodeficiency virus infection as a cause of IgA vasculitis.

BACKGROUND: Human immunodeficiency virus (HIV) has a protean clinical picture, in rare instances manifesting as systemic autoimmune disorders such as vasculitides. HIV-induced autoimmune diseases often do not respond well to systemic immunosuppressive therapy. Opportunistic infections may occur in patients with either acquired immunodeficiency syndrome (AIDS) or heavy immunosuppressive treatment, and can further complicate the clinical presentation. CASE PRESENTATION: A patient presenting with immunoglobulin A (IgA) vasculitis (IgAV) with treatment-refractory purpuric skin rash and suspect intestinal vasculitis was discovered to have AIDS. HIV was the trigger of IgAV, and cytomegalovirus (CMV) colitis mimicked intestinal vasculitis. Antiretroviral treatment improved both CMV colitis and the control of the autoimmune disease. CONCLUSIONS: An autoimmune disease relapsing despite adequate immunosuppressive treatment and/or the presence of recurrent severe opportunistic infections may be clues to an underlying HIV infection.

Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon γ in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA-DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.

Immunosuppressive treatments selectively affect the humoral and cellular response to SARS-CoV-2 in vaccinated patients with vasculitis.

OBJECTIVES: To analyse humoral and cellular immune response to mRNA COVID-19 vaccines in patients with GCA. METHODS: Consecutive patients with a diagnosis of GCA receiving two doses of BNT162b2 vaccine were assessed at baseline and 3 weeks from the second vaccine dose. Healthy subjects (n = 51) were included as controls (HC). Humoral response was assessed with Spike-specific IgG antibody response (S-IgG) and neutralizing antibodies (NtAb). Specific T cell response was assessed by enzyme linked immunosorbent spot (ELISpot). RESULTS: Of 56 included patients with GCA, 44 were eligible after exclusion of previous evidence of COVID-19 and incomplete follow-up. A significant proportion of patients with GCA (91%) demonstrated antibody (S-IgG) response, but this was significantly lower than HCs (100%); P < 0.0001. Neutralizing activity was not detected in 16% of patients with GCA. Antibody titres (S-IgG and NtAb) were significantly lower compared with HCs. Humoral response (S-IgG and NtAb) was significantly hampered by treatment with MTX. Cellular response was lacking in 30% of patients with GCA (vs 0% in HCs; P < 0.0001). Cellular response was significantly influenced by the levels of baseline peripheral T-lymphocytes and by glucocorticoid treatment. Treatment with tocilizumab did not affect any level of the immune response elicited by vaccination. CONCLUSIONS: Although patients with GCA apparently achieve a robust antibody seroconversion, there is a significant impairment of the neutralizing activity. MTX significantly reduced all levels of the humoral response. Up to one-third of patients do not develop a cellular immune protection in response to COVID-19 vaccination.

Fast-Track Ultrasound Clinic for the Diagnosis of Giant Cell Arteritis Changes the Prognosis of the Disease but Not the Risk of Future Relapse.

Background: Color Duplex sonography (CDS) of temporal arteries and large vessels (LV) is a recently validated diagnostic methodology for Giant Cell Arteritis (GCA). CDS combined with a fast-track approach (FTA) has improved the early diagnosis of the disease. Objectives: To assess FTA effects on the prevention of permanent visual loss (PVL), relapse and late complications of GCA compared to conventional practice. To assess the impact of COVID-19 pandemic on outcomes of GCA patients assessed with FTA. Methods: GCA patients diagnosed up to June 2020 at the Rheumatology Department, University of Pavia, were included. FTA was implemented since October 2016. FTA consists in the referral within 1 working day of a suspected GCA case to an expert rheumatologist who performs clinical evaluation and CDS. Results: One hundred sixty patients were recruited [female 120 (75%), mean age 72.4 ± 8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. FTA patients were older (75.1 ± 7.6 vs. 70.6 ± 8.2 years old; p < 0.001). Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p < 0.001). There was no difference between the two cohorts regarding major vessel district involvement (LV-GCA 17.5% vs. 22.7%; p = 0.4). PVL occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p = 0.03). The relative risk of blindness in the conventional group was 2.11 (95% C.I. 1.02-4.36; P = 0.04) as compared to FTA. Median symptom latency of patients experiencing PVL was higher in the conventional group (23 days IQR 12-96 vs. 7 days IQR 4-10, p = 0.02). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction (P = 0.2). No difference in late complications (stenosis/aneurysms) was detected. Conclusions: FTA including CDS evaluation contributed to a substantial reduction of PVL in GCA by shortening the time to diagnosis and treatment initiation. Relapse rate did not change upon FTA introduction, highlighting the need for better disease activity monitoring and treatment strategies optimization based on risk stratification that would predict the occurrence of relapse during glucocorticoid de-escalation.