Tocilizumab for the Treatment of Mevalonate Kinase Deficiency.

Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor quality of life, and life-threatening sequelae if inadequately treated. We report the case of a 12-year-old girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF- blockade.

Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.

Background: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares.

Methods: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab.

Increased platelet reactivity as measured by plasma glycoprotein VI in gout.

Patients with gout have an increased risk of cardiovascular events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets and megakaryocytes, is proteolytically cleaved upon platelet activation, and detectable in plasma as soluble GPVI (sGPVI). Therefore, elevated sGPVI is a marker of platelet activation and a risk marker for cardiovascular events.

Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1.

The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right.

Therapeutic blockade of interleukin-6 by tocilizumab in the management of AA amyloidosis and chronic inflammatory disorders: a case series and review of the literature.

Objectives: AA amyloidosis is the most serious potential complication of chronic inflammatory disorders. The main aim of treatment is to suppress inflammation thereby inhibiting serum amyloid A protein (SAA), which is the precursor of AA amyloid fibrils, to prevent or halt amyloid deposition. Interleukin (IL)-6 blockade is frequently effective in inflammatory conditions, however, there are few published data on its use in AA amyloidosis or the systemic autoinflammatory diseases (SAIDs) or chronic inflammatory conditions.

Impaired bone morphogenetic protein receptor II signaling in a transforming growth factor-β-dependent mouse model of pulmonary hypertension and in systemic sclerosis.

Rationale: Up to 10% of patients with systemic sclerosis (SSc) develop pulmonary arterial hypertension (PAH). This risk persists throughout the disease and is time dependent, suggesting that SSc is a susceptibility factor. Outcome for SSc-PAH is poor compared with heritable or idiopathic forms, despite clinical and pathological similarities.

Systemic sclerosis.

Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patient-to-patient variability. Like other autoimmune diseases, systemic sclerosis occurs more frequently in women, with a peak of onset in the fifth decade of life. The exact cause of systemic sclerosis remains elusive but is likely to involve environmental factors in a genetically primed individual.

p185, an immunodominant epitope, is an autoantigen mimotope.

An immunodominant peptide (p185(378-394)) derived from the c-erbB2 gene product, was recognized by an anti-DNA antibody, B3, and importantly by two classical DNA-binding proteins, Tgo polymerase and Pa-UDG. These reactivities were inhibited by DNA, confirming that the peptide mimicked DNA. BALB/c mice immunized with p185(378-394) developed significant titers of IgG anti-dsDNA antibodies.

Prevalence, serological features, response to treatment and outcome of critical peripheral ischaemia in a cohort of lupus patients.

Objective: This study addresses the issue of risk factors and management of critical peripheral ischaemia (CPI) and gangrene in SLE and proposes rituximab as a novel therapy.

Method: We conducted a retrospective study of 485 patients with SLE attending a UK tertiary referral centre, followed up over 27 yrs. Demographics, clinical features, serological features, treatment and outcome data were assessed.