Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria.

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.

HLA-DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin-1 in a transgenic mouse model.

Toxic shock syndrome toxin-1 (TSST-1) is a potent superantigen produced by Staphylococcus aureus. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST-1 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC) class II molecules and then activate a large proportion of T cells by cross-linking their T cell receptor. As binding to MHC class II molecules is a critical step in the robust activation of the immune system by TSST-1 and other superantigens, polymorphic variations between different HLA-DR alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST-1. As TSST-1 is highly toxic to humans and given that multiple variations of alleles of HLA-DR and HLA-DQ are expressed in each individual, it is difficult to determine how HLA-DR polymorphisms quantitatively and qualitatively impact immune activation caused by TSST-1 in humans. However, such investigations can be conducted on transgenic mice lacking all endogenous MHC class II molecules and expressing specific HLA class II alleles. Therefore, transgenic mice expressing different HLA-DRB1 alleles (HLA-DRB1*15:01, HLA-DRB1*15:02, HLA-DRB1*03:01, HLA-DRB1*04:01), and sharing HLA-A1*01:01 chain, were systemically challenged with purified TSST-1 and multiple immune parameters were assessed. Among the HLA-DR alleles, mice expressing HLA-DRB1*15:01 allele elicited a significantly higher serum cytokine/chemokine response; greater splenic T cell expansion and most severe organ pathology. Our study highlights the potential utility of human leukocyte antigen (HLA) transgenic mice in understanding the impact of HLA polymorphisms on the outcomes of diseases caused by TSST-1 and other superantigens.

Characterization of haemorrhagic pulmonary capillaritis: another manifestation of Pristane-induced lupus.

OBJECTIVES: Pristane-induced lupus is a well-established model of murine lupus. Mice injected with Pristane develop lupus-specific autoantibodies and glomerulonephritis. A chance observation led us to identify and characterize haemorrhagic pulmonary capillaritis in Pristane-injected mice. METHODS: Eight-week-old C57Bl/10 (B10, H-2(b)) mice received a single intraperitoneal injection of 0.5 ml of Pristane. Control mice received phosphate-buffered saline (PBS) injection. Mice were bled at 2 weeks after Pristane injection and monthly thereafter for serology and for antinuclear antibody (ANA). To characterize pulmonary disease, bronchoalveolar lavage (BAL) was carried out for total and differential cell count. Cytokines levels were checked for IL-2, IL-4, TNF-alpha, IFN-gamma, IL-6 and IL-10. Lungs were examined by histopathology and electron microscopy. RESULTS: All mice injected with Pristane developed a pulmonary capillaritis with perivascular infiltration with macrophages, neutrophils, lymphocytes and eosinophils. In addition, alveoli showed macrophage and neutrophil infiltration. The degree of perivascular and alveolar inflammation was moderate to severe. BAL was inflammatory with cell composition of macrophages, neutrophils, lymphocyte and eosinophils. There was evidence of endothelial injury on electron microscopy but no evidence of immune complex deposition. IL-6 and IL-10 were increased in BAL but levels of TNF-alpha, IFN-gamma, IL-2 and IL-4 were not. Anti-neutrophil cytoplasm antibody (ANCA) was negative. Kidneys demonstrated an increase in mesangial matrix and cellularity compatible with WHO Class II lupus lesion. There were immune complexes and complement deposition in the kidney. There were oil granulomas in peritoneum, spleen and liver but no evidence of vasculitis in these organs was seen. CONCLUSION: The relative ease and high penetrability of lesion makes it an attractive model to study pulmonary vasculitis.