Leishmania donovani: Immune response and immune evasion with emphasis on PD-1/PDL-1 pathway and role of autophagy

Leishmania donovani is one of the causative agents of visceral leishmaniasis. The immune response against Leishmania depends on CD4+ T helper type 1 cells. The immune system is unable to combat Leishmania because the parasite can exert several immune suppressive mechanisms that facilitate escaping the immune responses. One of these mechanisms is the up-regulation of programmed death-1/programmed death ligand-1 pathway which causes T cells to undergo exhaustion. Autophagy is strongly linked to the immune response, with some research indicating that activating autophagy reduces the immune response to some intracellular pathogens, while others indicate that activating autophagy limits the growth of intracellular pathogens. Leishmania was found to subvert the host defense mechanisms for its own persistence, such as Leishmania-induced autophagy modulation. Leishmania was reported to activate autophagy in different studies, thus getting a dual benefit by evading the immune system and simultaneously utilizing the autophagy byproducts as nutrients. In this review, we introduced different immune evasion/suppressive mechanisms used by Leishmania, and different immunotherapies which were developed accordingly. We focused on the programmed death-1/programmed death ligand-1 pathway as well as autophagy with the potential interplay of both mechanisms.

Osteoprotegerin in rheumatoid arthritis

Objective: To evaluate serum and synovial fluid levels of osteoprotegerin [OPG] in patients with rheumatoid arthritis [RA]; to correlate these values with disease activity variables, radiological bone damage, and DEXA results

Methodology: Twenty female RA patients and ten age-matched healthy female subjects were enrolled in this study. Serum and synovial fluid OPG levels were measured using enzyme-linked immunosorbent assay. Bone status was evaluated using dual x-ray absorptiometry [DEXA] and plain X-ray of the affected joints

Results: RA patients had significantly higher levels of serum OPG than controls [p<0.001]. No significant correlation was found between serum OPG and erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and disease duration [p>0.05]. OPG serum levels were positively correlated with age in both groups [p<0.001]. A significant difference in serum OPG level was found between patients with and without erosions [p=0.008]. RA patients had significantly lower BMD values than controls [p< 0.05]. There was a highly significant correlation between serum OPG level and BMD values [p<0.001]. Mean synovial fluid. OPG level was higher than serum OPG level obtained from the same patient, but with no statistical significance [p>0.05]

Conclusion: Bone loss in RA patients is associated with higher serum and synovial fluid levels of OPG than in healthy subjects, which might be the result of a compensatory production of OPG, yet there was lack of compensatory age-related increase of OPG serum levels

Detection of specific secretory IGA in saliva and stool of patients for diagnosis of Schistosoma mansoni infection

A total of thirty enzyme-linked immunosorbent [ELISA] assays detecting serum and secretory immunoglobulins against Schistosoma mansoni cercarial antigen preparation [CAP], soluble egg antigen [SEA], and adult worm antigen [AWA] were evaluated for diagnosis of Schistosoma mansoni infections. For each antigen, serum IgM, IgG, IgA, IgE, IgG1, IgG2 and IgG4 and secretory IgA in unstimulated saliva, stimulated saliva arid stool were quantitatively determined in samples from 116 Schistosoma mansoni infected subjects and 50 normal controls. Cut off values and evaluation parameters were calculated from receiver operating characteristic [ROC] curve. With serum samples, CAP-IgG, CAP-IgG1, SEA-IgG, SEA-IgG1, AWA-IgG1 and AWA-IgG4 were the best assays showing sensitivities of 94.8, 91.4, 95.7, 94.8, 91.4, and 94.8%, respectively, and specificities of 100, 92, 96, 100, 92, and 100%, respectively. With secretory IgA, stimulated saliva SEA and AWA-IgA, and stool SEA-IgA showed the best results with sensitivities of 85.4, 93.1, and 89.7%, respectively, and specificities of 100, 92, and 96%, respectively. In conclusion, different antibody classes determined showed high sensitivities and specificities in diagnosis of active schistosomiasis. Secretory IgA against Schistosoma mansoni antigens showed promising sensitivities and specificities, which make it a helpful tool in diagnosis of active schistosomiasis in the future, as it is an easy non invasive technique, which may help in epidemiological studies