Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers

Background and objectives: Interferon-a (IFN-a), a cytokine with both antiviral and immune-regulatory functions, was suggested as a useful tool which can evaluate current systemic lupus erythematosus (SLE) disease activity and identify patients whoare at risk of future disease flares. In the current study, serum IFN-a levels and associated demographic, and serological features in Egyptian SLE patients and their first degree relatives (FDRs) in comparison to unrelated healthy controls (UHCs) were examined, in order to identify individuals at the greatest risk for clinical illness.Methods: In a cross-sectional study, blood samples were drawn from 54 SLE patients, 93 of their FDRs who consented to enroll into the study and 76 UHCs. Measurement of serum IFN-a by a modified ELISA was carried out. Data were analyzed for associations of serum IFN-a levels with autoantibodies titer.Results: Meanserum IFN-a inFDRswas statistically higher than theUHCsand lower than inSLE patients (P < 0.0001) and it was correlated with ANA titer (r = 0.6, P < 0.0001) and anti ds DNA titer (r = 0.62, P < 0.0001).Conclusion: IFN-a is a crucial player in the complicated autoimmune changes that occur in SLE and serum IFN-a can be a useful marker identifying persons who are at risk of future disease development.Keywords: Interferon-a; Systemic lupus erythematosus; First degree relatives; Autoantibodie

Receptor-defined subtypes of breast cancer in indigenous populations in Africa: a systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa. METHODS AND FINDINGS: Medline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n=12,284 women with breast cancer) and 26 from sub-Saharan Africa (n=4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%-17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%-17%) lower for those with ≥ 40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56-0.62) and 0.21 (0.17-0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study. CONCLUSIONS: The published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost. Please see later in the article for the Editors' Summary