Objective
Autoantibodies against CD74 (anti‐CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, ...was undertaken to compare the sensitivity and specificity of anti‐CD74 and HLA–B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA).
Methods
Patients ages 18–45 years with inflammatory back pain of ≤2 years’ duration and a clinical suspicion of axSpA were recruited. HLA–B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty‐nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed.
Results
One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti‐CD74 and IgG anti‐CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti‐CD74 and IgG anti‐CD74 was 95.3%. The sensitivity of HLA–B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti‐CD74), 3.6 (IgG anti‐CD74), and 8.1 (HLA–B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti‐CD74, 15.3% for IgG anti‐CD74, and 28.8% for HLA–B27. A combination of IgA anti‐CD74 and HLA–B27 results in a posttest probability of 80.2%.
Conclusion
IgA anti‐CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation.
Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role ...of chemokines and their receptors in viral infections including HIV‐1 was predicted from the early studies of HIV‐1 co‐receptor CCR5 and its ligands and a divergent role of C‐C chemokines in HIV‐1 pathogenesis has been established. For example, CCL3 (MIP‐1α), CCL4 (MIP‐1β) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV‐1 co‐receptor CCR5, whereas CCL2, a pro‐inflammatory chemokine, supports HIV‐1 replication despite being a member of same chemokine family. Furthermore, the well‐established role of CCL2 in driving the Th2 immune response supports its potential role in HIV‐1/AIDS. Recent reports suggest multiple pathways of CCL2 affect HIV‐1 infection. In this review, we provide a comprehensive overview of the role and potential mechanisms of the HIV‐1‐CCL2 interplay in driving virus‐induced immuno‐pathology, suggesting that CCL2 could be an anti‐inflammatory target in the treatment of HIV‐1 infection.
Reduced CD73 on T cells in HIV correlates with disease progression, as well as functional CD8+ T cell defects, and is partially reversible by ART.
Recent studies indicate that murine Tregs highly ...express the ENTDP1, as well as the 5′‐NT and thereby, suppress Teff function by extracellular adenosine production. Furthermore, CD73 seems to play a role as costimulatory molecule for T cell differentiation. In this study, we analyzed the expression of CD73 on peripheral and lymph nodal Teffs and Tregs in a cohort of 95 HIV patients at different stages of disease, including LTNP and ECs. In contrast to murine Tregs, CD73 was only expressed on a small minority (∼10%) of peripheral Tregs. In contrast, we see high expression of CD73 on peripheral CD8+ T cells. In HIV infection, CD73 is markedly reduced on all Teffs and Tregs, regardless of the memory subtype. On CD8+ T cells, a positive correlation between CD73 expression and CD4 counts (P=0.0003) was detected. CD73 expression on CD8+ T cells negatively correlated with HLA‐DR (<0.0001) and PD1 (P=0.0457) expression. The lower CD73 expression on CD8+ T cells was partially reversible after initiation of ART (P=0.0016). Functionally, we observed that CD8+CD73+ T cells produce more IL‐2 upon HIV‐specific and unspecific stimulation than their CD73− counterparts and show a higher proliferative capacity. These data indicate that down‐regulation of CD73 on CD8+ T cells correlates with immune activation and leads to functional deficits in HIV infection.
Monocytes are known to engage in reciprocal crosstalk with NK cells but their influence on NK‐cell‐associated antibody‐dependent cellular cytotoxicity (ADCC) is not well understood. We demonstrate ...that in humans FcγRIII (CD16)‐dependent ADCC by NK cells is considerably enhanced by monocytes, and that this effect is regulated by FcγRII (CD32) crosslinking in healthy individuals. It is known that during HIV‐1 infection, NK cells are known to express low levels of CD16 and exhibit reduced ADCC. We show that immune regulation of CD16‐mediated NK‐cell cytotoxicity by monocytes through CD32 engagement is substantially disturbed in chronic progressive HIV‐1 infection. Expression of activating isoform of CD32 represented a compensatory mechanism for reduced expression of CD16 on NK cells during HIV‐1 infection. As a result, the regulation of NK‐cell‐associated ADCC by monocytes is skewed and eventually constitutes a novel factor that contributes to HIV‐1‐associated immune deficiency, dysregulation and pathogenesis. Our data therefore provide evidence, for the first time, that in humans monocytes act as a rheostat for FcγRIII‐mediated NK‐cell functions maintaining a well‐balanced immune response.
ObjectiveTo determine the non-inferiority of nurse-led care (NLC) in patients with anticitrullinated protein antibody (ACPA)-positive and/or rheumatoid factor (RF)-positive rheumatoid arthritis (RA) ...with active disease who are starting disease-modifying antirheumatic drug therapy, following treat-to-target (T2T) recommendations.MethodsA multicentre, pragmatic randomised controlled trial was conducted to assess clinical effectiveness, anxiety, depression and patient satisfaction following a non-inferiority design. The participants were 224 adults with ACPA/RF-positive RA who were randomly assigned to either NLC or rheumatologist-led care (RLC). The primary outcome was the Disease Activity Score in 28 Joints measured with C reactive protein (DAS28-CRP) assessed at baseline and after 3, 6, 9 and 12 months. A DAS28-CRP difference of 0.6 was set as the non-inferiority margin. Mean differences between the groups were assessed following per-protocol and intention-to-treat strategies.ResultsDemographic data and baseline characteristics of patients in the NLC group (n=111) were comparable to those of patients in the RLC group (n=113). The improvement in disease activity (change in DAS28-CRP, primary outcome) over the course of 12 months was significant in both groups (p<0.001). No significant differences were observed between the NLC and RLC groups (p=0.317). Non-inferiority of NLC was shown for the primary outcome and all secondary outcomes.ConclusionThis study supported the non-inferiority of NLC in managing T2T and follow-up care of patients with RA with moderate to high disease activity and poor prognostic factors in addition to RLC.Trial registration numberDRKS00013055.
HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection ...and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.
NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell ...phenotype and functionality mainly focusing on CD56(dim)CD16⁺ and CD56⁻CD16⁺ NK cells. However, the impact of HIV-infection on CD56(bright) NK cells is less well understood. Here we report a rise of CD56(bright) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7⁻CD56(bright) NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56(dim)CD16⁺ NK cells. Furthermore, CD56(bright) NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56(bright) NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.
Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of ...CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population.
A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals.
NK cells were analyzed by flow cytometry. Degranulation was assessed by measuring their expression of CD107a after stimulation with K562 cells, interleukin-12 and interleukin-15.
CD56(-)/CD16(+) NK cells are heterogeneous and composed of two populations, namely CD122(-)/CCR7(+) cells and CD122(-)/CCR7(+) cells. We show that expanded CD122(+) but not CCR7(+) cells in HIV-seropositive individuals are characterized by expression of senescence marker CD57 similarly to CD56(dim)/CD16(+) NK cells along with expression of KIRs, CD8, perforin and granzyme B. Despite expression of perforin and granzyme B, CD57 expressing cells exhibited less numbers of degranulating cells as measured by CD107a, indicating their functional impairment. However, there was no correlation between expansion of total CD56(-)/CD16(+) NK cells or the distinct subpopulations and viral load or CD4 cell count.
These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.
PDF
