Immune responses to mRNA-based vaccines given as a third COVID-19 vaccine dose in people living with HIV-a literature review.

People living with HIV (PLWH) were not included in the first efficacy studies of mRNA vaccines against SARS-CoV-2. In this literature review, we investigate evidence of humoral and cellular immunity after a third dose of an mRNA vaccine in PLWH. We performed a literature search in PubMed, Embase, Web of Science and SCOPUS published between 1 January 2020 and 31 December 2022. Selection criteria were studies on immunological responses in PLWH, who were given an mRNA-based vaccine as a third vaccine dose against SARS-CoV-2. Eight articles complied with our selection criteria. All studies found a strong humoral response after the third dose. Five studies investigated cellular immunity and found an increased cellular response after the third vaccine dose in PLWH. No difference in humoral response was observed between PLWH and controls after three doses. However, some of the studies suggested a weaker cellular response among PLWH than in controls, which was associated with lower nadir or current CD4+ T-cell counts. In conclusion, we found evidence of strong humoral immunity in PLWH after receiving an mRNA-based COVID-19 vaccine as a third dose, while the cellular immunity may be impaired compared to controls.

Humoral immune response to COVID-19 vaccine in patients with myasthenia gravis.

We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this to the response in healthy individuals. The SARS-CoV-2 IgG response and neutralizing capacity were measured in 83 patients (57 on immunosuppressants) and 332 healthy controls at baseline, three weeks, and two and six months after the vaccine. We found that the proportion of positive humoral response was lower in patients on immunosuppressants vs. controls at three weeks and two months (p ≤ 0.001), but not at six months post-vaccination (p = 0.379).

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk.

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.

Mpox Incidence and Vaccine Uptake in Men Who Have Sex with Men and Are Living with HIV in Denmark.

(1) Background: Here, we investigate the incidence of mpox and factors associated with vaccine uptake in mainly well-treated men who have sex with men and are living with HIV (MSMWH). (2) Methods: This study included 727 MSMWH from the Copenhagen co-morbidity in HIV infection (COCOMO) study from 1 May to 31 October 2022. Mpox infection and vaccination status were obtained from the Danish Microbiology Database and The Danish Vaccination Register. Vaccination willingness was assessed through an online survey. (3) Results: At a median follow-up of 180 days, 13 (1.8%) participants had laboratory-confirmed mpox infections. Furthermore, 238 (32.7%) had received the mpox vaccine. A sexually transmitted disease (STD) in the preceding two years was associated with a higher risk of mpox infection (hazard ratio 7.1; 95% confidence interval (CI) [1.9-26.9]) and with higher odds of vaccination (adjusted odds ratio 3.1; 95% CI [2.2-4.6]). 401 (55.2%) participants responded to the survey. 228 (57.0%) reported very high vaccination willingness. The self-perceived risk of infection was associated with vaccine uptake. (4) Conclusions: The incidence of mpox was low. A prior STD was associated with both a higher risk of mpox infection and higher odds of vaccination. Despite high-risk sexual behavior and high vaccination willingness, a sizable fraction of participants had not been vaccinated.

Humoral and cellular immune responses eleven months after the third dose of BNT162b2 an mRNA-based COVID-19 vaccine in people with HIV - a prospective observational cohort study.

BACKGROUND: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls. METHODS: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions. FINDINGS: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54-0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75-1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69-1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71-1.60), p = 0.767). INTERPRETATION: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine. FUNDING: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

Short-Lived Antibody-Mediated Saliva Immunity against SARS-CoV-2 after Vaccination.

Knowledge about the effect of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on immunity reflected in the saliva is sparse. We examined the antibody response in saliva compared to that in serum 2 and 6 months after the first vaccination with the BNT162b2 vaccine. Four hundred fifty-nine health care professionals were included in a prospective observational study measuring antibody levels in saliva and corresponding serum samples at 2 and 6 months after BNT162b2 vaccination. Vaccinated, previously SARS-CoV-2-infected individuals (hybrid immunity) had higher IgG levels in saliva at 2 months than vaccinated, infection-naive individuals (P < 0.001). After 6 months, saliva IgG levels declined in both groups (P < 0.001), with no difference between groups (P = 0.37). Furthermore, serum IgG levels declined from 2 to 6 months in both groups (P < 0.001). IgG antibodies in saliva and serum correlated in individuals with hybrid immunity at 2 and 6 months (ρ = 0.58, P = 0.001, and ρ = 0.53, P = 0.052, respectively). In vaccinated, infection-naive individuals, a correlation was observed at 2 months (ρ = 0.42, P < 0.001) but not after 6 months (ρ = 0.14, P = 0.055). IgA and IgM antibodies were hardly detectable in saliva at any time point, regardless of previous infection. In serum, IgA was detected at 2 months in previously infected individuals. BNT162b2 vaccination induced a detectable IgG anti-SARS-CoV-2 RBD response in saliva at both 2 and 6 months after vaccination, being more prominent in previously infected than infection-naive individuals. However, a significant decrease in salivary IgG was observed after 6 months, suggesting a rapid decline in antibody-mediated saliva immunity against SARS-CoV-2, after both infection and systemic vaccination. IMPORTANCE Knowledge about the persistence of salivary immunity after SARS-CoV-2 vaccination is limited, and information on this topic could prove important for vaccine strategy and development. We hypothesized that salivary immunity would wane rapidly after vaccination. We measured anti-SARS-CoV-2 IgG, IgA, and IgM concentrations in saliva and serum in both previously infected and infection-naive individuals, 2 and 6 months after first vaccination with BNT162b2, in 459 hospital employees from Copenhagen University Hospital. We observed that IgG was the primary salivary antibody 2 months after vaccination in both previously infected and infection-naive individuals, but dropped significantly after 6 months. Neither IgA nor IgM was detectable in saliva at either time point. Findings indicate that salivary immunity against SARS-CoV-2 rapidly declines following vaccination in both previously infected and infection-naive individuals. We believe this study shines a light on the workings of salivary immunity after SARS-CoV-2 infection, which could prove relevant for vaccine development.

Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study.

BACKGROUND: mRNA-based COVID-19 vaccines have short- and long-term efficacy in healthy individuals, but their efficacy in patients with psoriasis receiving immunomodulatory therapy is less studied. OBJECTIVES: To investigate long-term immunity after COVID-19 vaccination in patients with psoriasis receiving immunomodulatory therapy. METHODS: A prospective cohort study including patients (n = 123) with psoriasis receiving methotrexate (MTX) or biologics and controls (n = 226). Only mRNA-based COVID-19 vaccines administered with standard intervals between doses were investigated. Markers of immunity included SARS-CoV-2 spike glycoprotein-specific IgG and IgA, neutralizing capacity, and interferon-γ release from T cells stimulated with peptides of the SARS-CoV-2 spike glycoprotein. RESULTS: The proportion of IgG responders was lower 6 months after vaccination in patients receiving anti-tumour necrosis factor (TNF) treatment compared with controls. Anti-TNF treatment was associated with lower IgG levels (ß = -0.82, 95% confidence interval -1.38 to -0.25; P = 0.001). The median neutralizing index was lower in the anti-TNF group [50% inhibition (interquartile range [IQR] 37-89)] compared with controls [98% inhibition (IQR 96-99)]; P < 0.001. Cellular responses were numerically lowest in the anti-TNF group. CONCLUSIONS: Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity; however, the clinical implications are unknown.

Humoral Immune Responses after an Omicron-Adapted Booster BNT162b2 Vaccination in Patients with Lymphoid Malignancies.

To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population.

Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors.

SARS-CoV-2 vaccines are crucial in controlling COVID-19, but knowledge of which factors determine waning immunity is limited. We examined antibody levels and T-cell gamma-interferon release after two doses of BNT162b2 vaccine or a combination of ChAdOx1-nCoV19 and BNT162b2 vaccines for up to 230 days after the first dose. Generalized mixed models with and without natural cubic splines were used to determine immunity over time. Antibody responses were influenced by natural infection, sex, and age. IgA only became significant in naturally infected. A one-year IgG projection suggested an initial two-phase response in those given the second dose delayed (ChAdOx1/BNT162b2) followed by a more rapid decrease of antibody levels. T-cell responses correlated significantly with IgG antibody responses. Our results indicate that IgG levels will drop at different rates depending on prior infection, age, sex, T-cell response, and the interval between vaccine injections. Only natural infection mounted a significant and lasting IgA response.

Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls.

Background: Previous studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls. Methods: We measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose. Results: In SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08-1.24 to 11.97 AU/ml, 95% CI 7.73-18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70-385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95-83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11-1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30-1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09-2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10-1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25-2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16-2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26-1.82, p < 0.001). Conclusion: Immune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.

Incidence of Positive Severe Acute Respiratory Syndrome Coronavirus Polymerase Chain Reaction After Coronavirus Disease 2019 Vaccination With up to 8 Months of Follow-up: Real-life Data From the Capital Region of Denmark.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccines are implemented worldwide in efforts to curb the pandemic. This study investigates the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT-PCR) test following BNT162b2 vaccination in a large real-life population in Denmark. METHODS: Vaccination status and positive SARS-CoV-2 RT-PCR results from adults in the Capital Region of Denmark (n = 1 549 488) were obtained from national registries. PCR testing was free and widely available. The number of positive PCR tests per individual at risk was calculated as weekly rates. Time to positive PCR test was modelled using Kaplan-Meier methods and hazard ratios (HRs) were calculated using Cox regression. RESULTS: A total of 1 119 574 individuals received the first dose of BNT162b2 and 1 088 879 received a second dose of BNT162b2. Individuals were followed up to 8.7 months after first dose (median: 5.5 months; interquartile ratio: 4.1-8.7). Rates of PCR-confirmed SARS-CoV-2 infection 2-4 months after the second dose were 0.21, 0.33, and 0.36 per 1000 individuals per week at risk for July, August, and September, respectively. Four or more months after the second dose, the rates were 0.56, 0.76, and 0.53 per 1000 individuals per week at risk for July, August, and September, respectively. HR of SARS-CoV-2 infection after the second dose was 0.2 (95% confidence interval, .05-.48; P = .001) for individuals with 8 months' follow-up. CONCLUSIONS: Individuals who received 2 doses of the BNT162b2 COVID-19 vaccine had a low risk of breakthrough infection after up to 8 months of follow-up. However, there was a tendency toward higher rates with longer follow-up.

Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection.

Introduction: We investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection. Methods: We included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers. Results: At 12th-month, the IgG geometric mean concentrations (GMCs) (P<0.001), IgA GMCs (P=0.003), and median IFN-γ (P<0.001) were lower in SOT recipients than in controls. However, in SOT recipients and controls with previous infection, the neutralizing index was 99%, and the IgG, and IgA responses were comparable. After adjustment, female-sex (aOR: 3.6, P<0.009), kidney (aOR: 7.0, P= 0.008) or lung transplantation (aOR: 7.5, P= 0.014), and use of mycophenolate (aOR: 5.2, P=0.03) were associated with low IgG non response. Age (OR:1.4, P=0.038), time from transplantation to first vaccine (OR: 0.45, P<0.035), and previous SARS-CoV-2 infection (OR: 0.14, P<0.001), were associated with low IgA non response. Diabetes (OR:2.4, P=0.044) was associated with T-cell non response. Conclusion: In conclusion, humoral and T-cell responses were inferior in SOT recipients without previous SARS-CoV-2 infection but comparable to controls in SOT recipients with previous infection.

Humoral response to two doses of BNT162b2 vaccination in people with HIV.

BACKGROUND: People with HIV (PWH) are at increased risk of severe COVID-19. We aimed to determine humoral responses in PWH and controls who received two doses of BNT162b2. METHODS: In 269 PWH and 538 age-matched controls, we measured IgG and neutralizing antibodies specific for the receptor-binding domain of SARS-CoV-2 at baseline, 3 weeks and 2 months after the first dose of BNT162b2. RESULTS: IgG antibodies increased from baseline to 3 weeks and from 3 weeks to 2 months in both groups, but the concentrations of IgG antibodies were lower in PWH than that in controls at 3 weeks and 2 months (p = 0.025 and <0.001), respectively. The IgG titres in PWH with a humoral response at 2 months were 77.9% (95% confidence interval [62.5%-97.0%], age- and sex-adjusted p = 0.027) of controls. CONCLUSIONS: Reduced IgG antibody response to vaccination with BNT162b2 was found in PWH, and thus increased awareness of breakthrough infections in PWH is needed.

Divergent effects on macrophage biomarkers soluble CD163 and CD206 in axial spondyloarthritis.

The chronic joint inflammation in axial spondyloarthritis (axSpA) is characterized by infiltration of activated macrophages. The haptoglobin-hemoglobin receptor CD163 and the mannose receptor CD206 are strongly expressed on M2c and M2a macrophages, respectively. We measured the soluble forms of the receptors (sCD163 and sCD206) in plasma (PL) in two axSpA cohorts. All patients fulfil the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA and/or the 1984 modified New York criteria for ankylosing spondylitis. The first cohort included anti-TNF-α treated patients with active axSpA (n = 30); the second cohort included patients in early disease stages (n = 38). Plasma sCD163 and sCD206 were both within the reference interval of healthy controls (HC), but sCD163 decreased slightly during anti-TNF-α treatment [baseline: 1.49 mg/L (IQR: 1.22-1.77 mg/L, 12 weeks: 1.29 (IQR: 1.09-1.57) mg/L, 20 weeks: 1.25 (IQR: 0.99-1.75) mg/L, 52 weeks: 1.39 (IQR: 1.15-1.78) mg/L], while sCD206 increased [baseline: 0.17 (IQR: 0.13-0.21) mg/L, 12 weeks: 0.19 (0.16-0.23) mg/L, 20 weeks: 0.20 (0.14-0.24) mg/L, 52: 0.19 (IQR: 0.14-0.23) mg/L], pointing toward a shift in polarization of involved macrophages. Plasma levels of sCD206 proved significantly higher in patients with early disease stages and definite radiological sacroiliitis (n = 10). This was not the case for sCD163. A significant increase in response to anti-TNF-α treatment, could suggest sCD206 as a marker of response to anti-TNF-α treatment, however, the potential for the two macrophage markers as diagnostic and prognostic indicators of disease in axSpA is weak.

Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity.

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients with an average symptom duration of 3 months. Patients were randomized to 12 months' methotrexate and placebo (PLA) or methotrexate and adalimumab (ADA) treatment, followed by open-label treatment with disease-modifying anti-rheumatic drugs (DMARD) and if needed, ADA. Disease activity was assessed at baseline and after 3, 6, 12 and 24 months. Baseline plasma level of sCD206 in treatment naïve RA patients was 0.33 mg/L (CI: 0.33-0.38 mg/L) corresponding to the upper part of the reference interval for healthy controls (0.10-0.43 mg/L). In the PLA group, sCD206 levels decreased after 3 months, but did not differ from baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved this decrease throughout the study period.

Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis.

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation and can be treated by inhibition of the proinflammatory cytokines TNF-α and IL-17A. IL-26 is considered a proinflammatory cytokine, predominantly related to Th17 cells. In the present study, we investigate IL-26 expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were stained for IL-26 and analyzed by fluorescence microscopy. Synovial fluid mononuclear cells, C-C motif chemokine receptor 6 memory Th17 cells, and fibroblast-like synoviocytes (FLSs) were isolated, and supernatants were analyzed for IL-26 content by ELISA. FLSs were further stained for IL-26 production and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma (P < 0.0001). Moreover, IL-26 expression was found in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA+ myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts (P = 0.02). In conclusion, IL-26 seems to be produced by myofibroblasts in the inflamed synovium and could be a possible facilitator of bone mineralization in SpA. KEY MESSAGES: IL-26 levels are higher in synovial fluid compared to plasma in spondyloarthritis. IL-26 was identified in axial facet joints of spondyloarthritis patients. Myofibroblasts from the spondyloarthritis synovium produce large amounts of IL-26. IL-26 induces bone mineralization in human osteoblasts.