The population pharmacokinetics (PK) of belimumab were characterized in 1,603 patients with systemic lupus erythematosus receiving belimumab 1, 4, 10, or 20 mg/kg doses in Phase 1-3 trials. Belimumab PK were well described with a linear two-compartment model, with clearance from the central compartment (CL). Belimumab exposure was approximately dose-proportional. The estimated population terminal half-life was 19.4 days and steady-state volume of distribution (Vss) was 5.29 L for the currently approved 10 mg/kg dose used in the Phase 3 trials, with an estimated CL of 215 mL/day. No effects of age, sex, race, disease activity, co-medications, or baseline characteristics on belimumab PK were found to alter exposure in a manner requiring dose adjustment. An association observed between increasing baseline proteinuria and increasing CL may be clinically relevant in nephropathy with very high proteinuria levels. No evidence of target-mediated clearance was observed. Clinically relevant effects of body size (increased CL and V1 with increased body weight, and reduced V1 with increased body mass index) have been accounted for in current weight-normalized belimumab dosing.

Severe retinal vascular occlusions resulting in blindness is a rare occurrence in patients with systemic lupus erythematosus (SLE). Herein, we report a case of a 33-year-old female who developed combined central retinal artery occlusion, retinal vein occlusion, and choroidopathy and rapidly became completely blind in both eyes within a week. The electroretinogram revealed a severely attenuated a-wave and b-wave, indicating a profound dysfunction of both choroidal and retinal circulation, respectively. The current case demonstrates objectively the functional impact of severe choroidopathy in SLE for the first time. Patients with unilateral blindness due to combined retinal/choroidal vascular obstructions should be monitored carefully to ensure adequate anticoagulant therapy in an attempt to guard the vision in the fellow eye.

Objective.

The Medical Outcomes Short Form-36 Survey (SF-36) has been widely used as a measure of health-related quality of life (HRQOL) in different populations. SLE patients have consistently reported lower scores compared with the general population. The objective of our study was to identify predictors of HRQOL using SF-36 among patients with SLE enrolled in a 2-year randomized controlled trial (RCT).Methods. We analysed 200 SLE patients enrolled in the Lupus Atherosclerosis Prevention Study (LAPS), an RCT of atorvastatin vs placebo, who completed SF-36 at qualifying, 12- and 24-month (final) visits.

Results.

At baseline, mean SF-36 domain scores were lower than those of age- and gender-matched population norms. There was no statistical difference reported between Physical Component Summary (PCS), Mental Component Summary and eight domain scores in the atorvastatin vs placebo group at 2 years. In multiple regression analyses, African American patients reported significantly lower scores in Physical Functioning compared with Caucasians. The presence of FM was significantly associated with lower scores in physical functioning, role physical, bodily pain, general health, vitality, social functioning and lower overall mean PCS scores. The Physician's Global Assessment of disease activity was associated with multiple SF-36 domains in univariate analysis.

Conclusion.

This longitudinal study confirmed lower scores reported across all SF-36 domains. No one explanatory variable was independently associated with all domain scores. FM was independently associated with poorer HRQOL in most domains, underscoring the need for effective treatments for FM in SLE.

Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes.

OBJECTIVE:

HLA-G has well recognized tolerogenic properties in physiological and nonphysiological conditions. The 3' untranslated region (3'UTR) of the HLA-G gene has at least 3 polymorphic sites (14-bpINS/DEL, +3142C/G, and +3196C/G) described as associated with posttranscriptional influence on messenger RNA production; however, only the 14-bpINS/DEL and +3142C/G sites have been studied in systemic lupus erythematosus (SLE).

METHODS:

We investigated the HLA-G 3'UTR polymorphic sites (14-bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, and +3196C/G) in 190 Brazilian patients with SLE and 282 healthy individuals in allele, genotype, and haplotype analyses. A multiple logistic regression model was used to assess the association of the disease features with the HLA-G 3'UTR haplotypes.

RESULTS:

Increased frequencies were observed of the 14-bpINS (p = 0.053), +3010C (p = 0.008), +3142G (p = 0.006), and +3187A (p = 0.013) alleles, and increased frequencies of the 14-bpINS-INS (p = 0.094), +3010 C-C (p = 0.033), +3142 G-G (p = 0.021), and +3187 A-A (p = 0.035) genotypes. After Bonferroni correction, only the +3142G (p = 0.05) and +3010C (p = 0.06) alleles were overrepresented in SLE patients. The UTR-1 haplotype (14-bpDEL/+3003T/+3010G/+3027C/+3035C/+3142C/+3187G/+3196C) was underrepresented in SLE (pcorr = 0.035).

CONCLUSION:

These results indicate that HLA-G 3'UTR polymorphic sites, particularly +3142G and +3010C alleles, were associated with SLE susceptibility, whereas UTR-1 was associated with protection against development of SLE.

INTRODUCTION:

Predicting thrombosis in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (aPL) is still challenging. Our objective was to determine risk factors for thrombotic events including activated protein C (APC) resistance proven by a thrombin generation (TG) assay in patients with SLE and/or aPL.

MATERIALS AND METHODS:

We performed a prospective cohort study in a French University Hospital and tertiary care center. Ninety-two consecutive patients with SLE and/or aPL without ongoing anticoagulant treatment were enrolled. The outcome was time to thrombotic event. We evaluated clinical and laboratory variables including APC sensitivity ratio (APCsr) determined by TG. An APCsr>90th percentile of a control population indicated APC resistance.

RESULTS:

Patients were followed-up for a median duration of 35months (inter-quartile range: 26 to 62; 320 patient-years). Thrombosis during follow-up occurred in 18 patients. In univariate analysis, together with history of hypertension, superficial vein thrombosis (SVT) and arterial thrombosis, patients with both aPL and APC resistance had an increased risk for incident thromboembolic events (HR, 3.67[95% confidence interval, 1.31 to 10.31]). In multivariate analysis, only history of hypertension (HR, 10.77 [95% confidence interval, 3.15 to 36.83]), SVT (HR, 7.45 [95% confidence interval, 2.25 to 24.66]) and arterial thrombosis (HR, 3.31 [95% confidence interval, 1.14 to 9.55]) remained independent risk factors.

CONCLUSIONS:

History of thrombosis including seemingly benign SVT have a higher predictive value for incident thrombotic events in SLE or aPL patients than APC resistance proven by TG.

Primary immune thrombocytopenia (ITP) is an organ-specific autoimmune disorder characterized by autoantibody-mediated enhanced platelet destruction and dysmegakaryocytopoiesis. B cells have been demonstrated to play critical roles in the pathophysiology of ITP. B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are crucial cytokines supporting survival and differentiation of B cells, and dysregulation of BAFF/APRIL is involved in the pathogenesis of B-cell related autoimmune diseases including ITP. Currently ongoing clinical trials using BAFF and/or APRIL-blocking agents have yielded positive results in human systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), further confirming the pathological role of BAFF/APRIL in autoimmunity. This review will describe the function of BAFF/APRIL and address the feasibility of BAFF/APRIL inhibition in the management of ITP.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by both accelerated clearance of autoantibody-sensitized platelets and suboptimal platelet production. A number of studies have provided evidence of disturbed innate and adaptive immune responses in patients with ITP. This brief review will highlight some of the more recent work in this field and highlight other findings that provide a potential link between ITP, systemic lupus erythematosus (SLE), and autoimmune hemolytic anemia (AHA).