Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease.

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.1,2 We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1+/- mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE.

Treatment of systemic lupus erythematosus.

Systemic lupus erythematosus should be suspected in individuals with one or more classic symptoms. Diagnosis is made clinically and supported by serology Reducing sun exposure is central to the management of lupus Hydroxychloroquine is first-line treatment unless contraindicated and is useful in almost all manifestations of lupus. Other treatments are titrated against type and severity of organ involvement Monoclonal antibodies have a limited role in the management of lupus

Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus.

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.

Are Elite Female Soccer Athletes at Risk for Disordered Eating Attitudes, Menstrual Dysfunction, and Stress Fractures?

OBJECTIVE: To determine the prevalence of stress fractures, menstrual dysfunction and disordered eating attitudes in elite female soccer athletes. DESIGN: Cross-sectional descriptive study. SETTING: Female soccer athletes were recruited from a national level youth soccer club, an NCAA Division I university team, and a women's professional team. PARTICIPANTS: Two hundred twenty female soccer athletes with a mean age of 16.4 ± 4 years and BMI of 20.8 ± 2 kg/m(2) completed the study, representing all athletes from the included teams. METHODS: One-time surveys completed by the athletes. MAIN OUTCOME MEASUREMENTS: Height and weight were recorded, and body mass index (BMI) was calculated for each athlete. Athletes reported age of menarche, history of missing 3 or more menses within a 12-month period and stress fracture. The Eating Attitudes Test (EAT-26) was used to assess the athlete's body perception and attitudes toward eating. RESULTS: Of the 220 soccer athletes, 3 athletes (1.6%) had a low BMI for their age, and 19 (8.6%) reported stress fractures of the lower extremity. Among athletes who had reached menarche, the average onset was 13 + 1 year; menstrual dysfunction were present in 21 (19.3%). On the EAT-26, 1 player scored in the high risk range (>20) and 17 (7.7%) scored in the intermediate risk range (10-19) for eating disorders. Athletes with an EAT-26 score ≥ 10 points had a significantly higher prevalence of menstrual dysfunction in the past year compared to athletes with an EAT-26 score of less than 10 (P = .02). CONCLUSIONS: Elite female soccer athletes are susceptible to stress fractures and menstrual dysfunction and have delayed onset of menarche despite normal BMI and appropriate body perception and attitudes towards eating. Further studies are needed to better understand stress fracture risk in female soccer athletes and in other team sports to determine how these findings relate to long-term bone health in this population.