ABSTRACT
Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Methods: Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. Results: A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70). Conclusion: By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Male , Lupus Nephritis/diagnosis , Lupus Nephritis/epidemiology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , AutoantibodiesABSTRACT
ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE.
Subject(s)
Asian People/genetics , CD11b Antigen/genetics , Disease Susceptibility , Lupus Erythematosus, Systemic/genetics , Nephritis/genetics , Adult , Asian People/ethnology , Case-Control Studies , Female , Genome-Wide Association Study , Hong Kong , Humans , Lupus Erythematosus, Systemic/ethnology , Male , Middle Aged , Nephritis/ethnology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Thailand , White People/genetics , Young AdultABSTRACT
A number of rheumatological diseases predominantly affect women of reproductive age. There has always been concern that the use of oestrogen-containing agents such as combined hormonal contraception and hormone therapy might aggravate these conditions. This article reviews the up-to-date evidence regarding the safety of using these agents in women with various rheumatological diseases, with emphasis on systemic lupus erythematosus and rheumatoid arthritis. In the absence of antiphospholipid antibody or other prothrombotic risk factors, combined hormonal contraception is not contra-indicated in most rheumatological conditions including inactive systemic lupus erythematosus. Moreover, hormone therapy is generally not contra-indicated except for women with active systemic lupus erythematosus disease where its effect on disease flare is less clear and individual judgement is required.