Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients

INTRODUCTION: The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaounde, Yaounde, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. Fifty-one patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls. RESULTS: An anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high positive predictive (PPV) (96%) and negative predictive values (NPV) (91%). Thirty percent of RA patients were carrying at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA. CONCLUSIONS: Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patient cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients

Non-infectious lupus pericarditis: a retrospective hospital-based observation in Yaounde-Cameroon

To determine the frequency of non-infectious lupus pericarditis in patients with systemic lupus erythematosus (SLE) seen in the Yaounde Central and General Hospitals. A descriptive retrospective study was carried out in Rheumatology Units of Yaounde Central and General Hospitals, from January 2001 to January 2004. Inclusion criteria: patients fulfilling the American College of Rheumatology criteria for SLE and presenting with pericarditis. The study consisted of 22 female and one male SLE patients with a mean age of 26 years (range=13-65). Ten out of 23 patients (43%) presented pericarditis with a mean duration of illness before the diagnosis of pericarditis of 2 years. Pericardial rub was the commonest sign (seven cases), followed by dyspnea (six cases) and chest pain (six cases). The diagnosis of pericarditis was proven by echocardiography in all cases. Typical serological findings included anti-nuclear antibodies, anti-double-stranded DNA, and anti-Sm antibodies. Chest X-ray revealed cardiomegaly in all the patients. Electrocardiogram showed abnormal repolarization (seven patients) and low voltage QRS complexes (three cases). Treatment consisted of steroids administration. Four patients had relapse of pericarditis during subsequent lupus flares. This short series shows that non-infectious pericarditis is common in SLE patients in Africa

In Black Africans with rheumatoid arthritis, ACPA recognize citrullinated fibrinogen and the derived peptides α36-50Cit38,42 and β60-74Cit60,72,74, like in Caucasians

Well documented in Caucasians and Asians, the diagnostic value of anti-CCP2 antibodies has been confirmed in Black African populations. However, autoantibodies to other citrullinated peptides/proteins and their fine specificities have not yet been studied. Here, we show that in Cameroonian patients, anti-citrullinated fibrinogen autoantibodies (AhFibA) are sensitive (73%) diagnostic markers for RA. We also determine that autoantibodies directed to α36-50Cit38,42 or β60-74Cit60,72,74 peptides which bear the immunodominant epitopes of citrullinated fibrin, are present in similar proportions in Black Africans and Caucasians with 25/56 (45%) and 41/56 (73%) positive RA-sera in Cameroonians, respectively. They also account for almost all the AhFibA reactivities since 38/41 (93%) AhFibA-positive sera contain anti-α36-50Cit38,42 and/or anti-β60-74Cit60,72,74 autoantibodies. Finally, HLA-DRB1 SE alleles were associated with higher titres of AhFibA and anti-β60-74Cit60,72,74 autoantibodies. In the genetic and environmental backgrounds of Black Africans, AhFibA are a hallmark of RA like in Caucasians, moreover they recognize the same fibrin epitopes

Systemic lupus erythematosus in native sub-saharan africans: a systematic review and meta-analysis

International audienceThe prevalence and phenotype of systemic lupus erythematosus (SLE) have not been thoroughly investigated in Native sub-Saharan Africans despite knowledge that the highest burden of SLE occurs in people with an African trait. Through this systematic review of literature and meta-analysis, we wished to fill this gap.PubMed, EMBASE, Web of Science, African Journals Online, and Global Index Medicus as well as references of retrieved papers were searched to select studies addressing SLE in Native sub-Saharan Africans and published between January 1, 2008 and October 7, 2018. The prevalence of SLE and its characteristics were pooled through narrative review and random-effects model. Heterogeneity (I22Out of 1502 papers, 15 hospital-based studies were included. The pooled prevalence of SLE among 28,575 participants was 1.7% (0.8-2.9), with substantial heterogeneity between studies (I2Over the last 30 years, SLE was not rare among Native sub-Saharan Africans and its featured characteristics were earlier onset, female predominance, and high seropositivity for extractable nuclear antigen autoantibodies. Corticosteroids and antimalarials were the standard treatments. The mortality rate was high. Population prevalence and incidence as well as full description of SLE characteristics in Native sub-Saharan Africans are needed

Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease

INTRODUCTION: The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans. METHODS: RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts. RESULTS: After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001. CONCLUSIONS: The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds

High C-reactive proteins levels, rheumatoid anemia, alpha-1 globulin deficiency, and hypergammaglobulinemia in rheumatoid arthritis patients from yaounde, Cameroon

Background: Rheumatoid arthritis (RA) is an autoantibodies-mediated disease affecting 0.5%–1% of the population worldwide. The present study was designed to investigate variations of protein profiles and hematological parameters of patients in Yaounde Central Hospital. Methods: The study was conducted from January to November 2017. RA cases were recruited based on the identification of established diagnosis from registers of patients of participating rheumatologists. Healthy volunteers visiting the hospital were also included as a control population. All participants were aged 15 years and above. Whole blood collected from each participant was assayed for hematological parameters. In addition, serum from each participant was assayed for the level of C-reactive proteins (CRPs) using a plate agglutination technique whereas plasma was used for protein profile through a conventional electrophoretic migration of proteins on cellulose acetate gel. Results: Overall, 22 RA patients and 10 controls were recruited and consisted, respectively, in 5 males and 17 females and 2 males and 8 females. Our study revealed that 59.09% (13/22) of patients presented high levels of CRP compared to 10% in the control group. The mean value of red blood cells was 4.38 × 106/μl and 4.698 × 106/μl, respectively, in the RA and the control groups. The mean hemoglobin value was significantly reduced in the RA group (11.07 mg/dl vs. 12.73 mg/dl, P = 0.0192), thus revealing anemia in patients. Nearly 54.5% of patients presented hypoalbuminemia compared to 20% in the control group (P = 0, 1241). A deficiency of α1-globulin was observed in 54.5% of patients while that of control group was 30%. Furthermore, 72% of the patient presented hypergammaglobulinemia compared to 30% in the control group (P = 0.0494). Conclusion: This study revealed that RA patients present a normochromic and normocytic anemia, a decreased albumin and alpha 1 globulin, a significant elevation of gamma-globulins compared to the control population

Women in rheumatology in Africa

Despite the increasing occurrence of rheumatic diseases worldwide, there is poor access to rheumatology services and few rheumatologists to provide these services in many regions of the world. This fact is particularly true in areas of lower socioeconomic status and low-income and middle-income countires. Studies across various countries show a relative shortage of rheumatologists compared with the rising need for the specialty worldwide

Comparative Performance of Serological (IgM/IgG) and Molecular Testing (RT-PCR) of COVID-19 in Three Private Universities in Cameroon during the Pandemic

Background: COVID-19 remains a rapidly evolving and deadly pandemic worldwide. This necessitates the continuous assessment of existing diagnostic tools for a robust, up-to-date, and cost-effective pandemic response strategy. We sought to determine the infection rate (PCR-positivity) and degree of spread (IgM/IgG) of SARS-CoV-2 in three university settings in Cameroon Method: Study volunteers were recruited from November 2020 to July 2021 among COVID-19 non-vaccinated students in three Universities from two regions of Cameroon (West and Centre). Molecular testing was performed by RT-qPCR on nasopharyngeal swabs, and IgM/IgG antibodies in plasma were detected using the Abbott Panbio IgM/IgG rapid diagnostic test (RDT) at the Virology Laboratory of CREMER/IMPM/MINRESI. The molecular and serological profiles were compared, and p p p p= 0.05, p = 0.05, and p = 0.01, respectively). Overall IgG seropositivity (IgM−/IgG+ and IgM+/IgG+) was 24.4% (71/291). A proportion of 26.92% (7/26) presenting COVID-19 IgM+/IgG− had negative PCR vs. 73.08% (19/26) with positive PCR, p p < 0.0001. Lastly, 7.22% (14/194) with IgM−/IgG− had a positive PCR. Conclusion: This study calls for a rapid preparedness and response strategy in higher institutes in the case of any future pathogen with pandemic or epidemic potential. The observed disparity between IgG/IgM and the viral profile supports prioritizing assays targeting the virus (nucleic acid or antigen) for diagnosis and antibody screening for sero-surveys

Comparative Performance of Serological (IgM/IgG) and Molecular Testing (RT-PCR) of COVID-19 in Three Private Universities in Cameroon during the Pandemic

Background: COVID-19 remains a rapidly evolving and deadly pandemic worldwide. This necessitates the continuous assessment of existing diagnostic tools for a robust, up-to-date, and cost-effective pandemic response strategy. We sought to determine the infection rate (PCR-positivity) and degree of spread (IgM/IgG) of SARS-CoV-2 in three university settings in Cameroon Method: Study volunteers were recruited from November 2020 to July 2021 among COVID-19 non-vaccinated students in three Universities from two regions of Cameroon (West and Centre). Molecular testing was performed by RT-qPCR on nasopharyngeal swabs, and IgM/IgG antibodies in plasma were detected using the Abbott Panbio IgM/IgG rapid diagnostic test (RDT) at the Virology Laboratory of CREMER/IMPM/MINRESI. The molecular and serological profiles were compared, and p &lt; 0.05 was considered statistically significant. Results: Amongst the 291 participants enrolled (mean age 22.59 &plusmn; 10.43 years), 19.59% (57/291) were symptomatic and 80.41% (234/291) were asymptomatic. The overall COVID-19 PCR-positivity rate was 21.31% (62/291), distributed as follows: 25.25% from UdM-Bangangte, 27.27% from ISSBA-Yaounde, and 5% from IUEs/INSAM-Yaounde. Women were more affected than men (28.76% [44/153] vs. 13.04% [18/138], p &lt; 0.0007), and had higher seropositivity rates to IgM+/IgG+ (15.69% [24/153] vs. 7.25% [10/138], p &lt; 0.01). Participants from Bangangt&eacute;, the nomadic, and the &ldquo;non-contact cases&rdquo; primarily presented an active infection compared to those from Yaound&eacute; (p= 0.05, p = 0.05, and p = 0.01, respectively). Overall IgG seropositivity (IgM&minus;/IgG+ and IgM+/IgG+) was 24.4% (71/291). A proportion of 26.92% (7/26) presenting COVID-19 IgM+/IgG&minus; had negative PCR vs. 73.08% (19/26) with positive PCR, p &lt; 0.0001. Furthermore, 17.65% (6/34) with COVID-19 IgM+/IgG+ had a negative PCR as compared to 82.35% with a positive PCR (28/34), p &lt; 0.0001. Lastly, 7.22% (14/194) with IgM&minus;/IgG&minus; had a positive PCR. Conclusion: This study calls for a rapid preparedness and response strategy in higher institutes in the case of any future pathogen with pandemic or epidemic potential. The observed disparity between IgG/IgM and the viral profile supports prioritizing assays targeting the virus (nucleic acid or antigen) for diagnosis and antibody screening for sero-surveys