Legalization of cannabis' medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently, evidence supports cannabis and its active ingredients as immune-modulating agents, affecting T-cells, B-cells, monocytes, and microglia cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease, and fibromyalgia suggest cannabis' effectiveness as an immune-modulator. However, contradicting results and lack of large-scale clinical trials obscure these results. Although lacking clinical research, in vitro and in vivo experiments in rheumatoid arthritis, diabetes type 1, and systemic sclerosis demonstrate a correlation between disease activity and cannabinoids.

Autoantibodies, which are antibodies that target self-epitopes, have considerable diagnostic, prognostic and predictive value in specific autoimmune diseases. Various infectious agents have been linked via numerous mechanisms to the formation of different autoantibodies. Therefore, estimating the prevalence of autoantibodies and anti-infectious antibodies in different populations is of high importance. Different genetic and environmental pressures, such as these found in Ghana's different geographical provinces, may affect the prevalence of autoantibodies. In this study, we assessed the seroprevalence of a diverse panel of autoantibodies and anti-infectious antibodies among the healthy Ghanaian population and investigated possible environmental and genetic predispositions for autoantibodies and autoimmunity. The sera of 406 healthy individuals were obtained from Greater Accra, Upper West, Eastern and Volta regions. Multiplexed assay and chemiluminescent immunoassay techniques were utilized to assess the presence of a panel of autoantibodies and anti-infectious antibodies. We found a high prevalence of anti-HSV-1 IgG (91-100%), anti-EBNA IgG (81-93%) and anti-EBV-VCA IgG (97-100%) antibodies. The prevalence of ANA (at least one of: anti-dsDNA; antichromatin; anti-ribosomal-P; anti-Ro/SSA; anti-La/SSB; anti-centromere B; anti-Sm; anti-Sm/RNP; anti-Scl-70; anti-Jo1; anti-DFS70) was estimated at 14%. An inverse association between anti-HSV-2 antibodies and ANA (p = 0.044; adjusted OR = 0.398; CI [0.162-0.975]) was found, after adjusting for differences in gender, age, and familial history of autoimmune diseases. A trend towards reduced seroprevalence of anti-dsDNA antibodies among subjects who were positive for anti-HSV-2 antibodies was also noted (p = 0.1). In conclusion, the inverse association between anti-HSV-2 antibodies and ANA positivity suggests a possible protective role of HSV-2 infection against autoimmunity.Currently, the etiology of autoimmune diseases (AIDs) is not completely understood. Many variables are thought to play a role in the development of these diseases, including genetic, immunological, hormonal and environmental factors 1 . These various factors and the interactions between them, which constitute the "Mosaic of Autoimmunity", may contribute to autoimmunity by different mechanisms. One of these mechanisms is associated with the loss of self-tolerance 2 .Infectious agents, which are members of the environmental pebble of the mosaic, can induce loss of tolerance through various mechanisms, such as: (1) Epitope spreading, i.e. development of an autoimmune response mediated by autoreactive T-cells and expansion of the auto-reactive B-cell repertoire to endogenous epitopes, following

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BACKGROUND/AIMS In the CYP3A5 gene, the A>G (*3) and G>A (*6) SNPs result in splicing defects and severely decreased expression of CYP3A5 enzyme. We tested whether these polymorphisms are associated with differences in response to verapamil, a calcium channel blocker that is a CYP3A substrate and inhibitor. METHODS All patients from the hypertension clinical trial INVEST for whom the only change to therapy at the initial visit was the addition of verapamil and who consented to genetic analysis were genotyped for CYP3A5*3 and *6 SNPs. CYP3A5 haplotypes were determined by PHASE II with any alleles containing either *3 (G) or *6 (A) designated as nonfunctional. The data were analyzed using SAS PROC GLM with baseline values, dose, ethnicity, age, height, weight and sex included in the model. RESULTS Allele frequencies for *3 (G) and *6 (A) were 0.30, 0.69, 0.90 and 0.15, 0.04, 0.0 for Blacks (n=36), Hispanics (n=252) and Whites (n=173), respectively. When controlled for baseline blood pressure (BP) values, there were significant differences in treated (Tx) diastolic BP (DBP), and mean BP (MBP) based on number of functional CYP3A5 alleles (Table), but not systolic BP (SBP). Findings remained significant when considering multiple covariates in the model, and in addition to CYP3A5 genotype, baseline BP, weight and ethnicity were also significant covariates for DBP and MBP response. Number of CYP3A5 functional Alleles Tx SBP Tx DBP Tx MBP 0 (n = 290)136 ± 1579 ± 998 ± 91 (n = 138)136 ± 1979 ± 998 ± 102 (n = 38)141 ± 2283 ± 9103 ± 12Overall p value0.130.0060.008 CONCLUSIONS These data suggest CYP3A5 genotypes may influence hemodynamic responses to verapamil. Clinical Pharmacology & Therapeutics (2005) 79, P12–P12; doi:

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BackgroundSarcoidosis is an inflammatory disease characterised by the hallmark sign of non-caseating granulomas1,2. In the past decade a consensus has formed regarding the pivotal role of inflammation in atherosclerosis3. Since this discovery the association between chronic inflammatory states and ischaemic heart disease was confirmed in several rheumatic diseases4. Therefore, the constant state of inflammation to which sarcoidosis patients are exposed might pose as a risk factor for ischaemic heart disease.ObjectivesThe aim of this study is to assess the relation between sarcoidosis and Ischaemic heart disease and its prognostic significance.MethodsBased on data from Clalit Health Services (CHS), Israel’s largest health maintenance organisation, the medical records of 3993 sarcoidosis patients and 19 856 controls were acquired. Controls were matched to sarcoidosis patients according to age and sex. Chi-square and student t-tests were used in order to compare variables distribution in the cohort. Variables associated with ischaemic heart disease were assessed by logistic regression model. Log-rank test was performed for survival analysis, while Cox proportional hazards method was utilised to evaluate variables related to increased risk of all-cause mortality.ResultsMatched by sex and age – both sarcoidosis group and the control group were composed from 63% females with mean age being 56 years. Compared to the control group, sarcoidosis patients had a higher proportion of ischaemic heart disease, presenting with 856 (21.4%) cases whereas the control group had only 2999 cases (15.1%, p<0.001). The association between sarcoidosis and ischaemic heart disease was demonstrated by a multivariate analysis, (adjusted OR 1.503, 95% CI 1.361–1.660). A 15 year follow up revealed increased mortality among sarcoidosis patients – as 710 (17.8%) of sarcoidosis patients had passed away while 2121 (10.7%) deaths were reported in the control group (p<0.001). In a multivariate model, sarcoidosis patients were found to be in increased risk for all-cause mortality compared to the control group (adjusted HR 1.95, 95% CI 1.75–2.14).ConclusionsSarcoidosis is associated with an increased risk for ischaemic heart disease and all-cause mortality. Patients with co-morbidity of sarcoidosis and ischaemic heart disease should be treated accordingly.References[1] Markevitz, N, Epstein Shochet G, Levi Y, Israeli-Shani L, Shitrit D. Sarcoidosis in Israel: Clinical Outcome Status, Organ Involvement, and Long-Term Follow-Up. Lung2017;195;419–424.[2] Valeyre D, et al. Sarcoidosis. Lancet (London, England)2014;383;1155–67.[3] Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation2004;109:II2–10.[4] Shoenfeld Y, et al. Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases. Circulation2005;112:3337–3347.Disclosure of InterestNone declared