Statins are one of the most commonly prescribed drugs in New Zealand, with 525 772 or 16.5% of the adult New Zealand population prescribed a statin between June 2013 and July 2014. While generally well-tolerated, statins are known to cause a range of muscle-related side effects, ranging from myalgia to life-threatening rhabdomyolysis. Recently, it has been recognised that in rare instances, statins can induce an immune-mediated necrotising myositis with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the enzymatic target of statins. In 2014, anti-HMGCR antibody testing was introduced to Canterbury Health Laboratories (CHL), with this being the only laboratory in New Zealand performing this test during the period of this case series. This article describes an index case and characterises the clinical features of a subsequent 12-month series. From this series, we estimated the yearly incidence of HMGCR-associated myositis at 1.7/million/year or ~1/90 000 New Zealand statin users.

The administration of Th2 cytokines or immune deviation to a Th2 phenotypic response has been shown to protect against the autoimmune pathology of experimental autoimmune encephalomyelitis (EAE). To better understand the function of Th2 cytokines in the induction stage of EAE in the absence of an overt Th2 response, we immunized IL-4 receptor alpha-deficient (IL-4Ra À/À ) mice, which are unable to respond to either IL-4 or IL-13. Contrary to expectations, mice lacking IL-4Ra had a lower incidence of EAE and a delayed onset compared to WT BALB/c mice; however, this delay did not correlate to an alteration in the Th1/Th17 cytokine balance. Instead, IL-4Ra-responsive macrophages were essential promoters of disease as macrophagespecific IL-4Ra-deficient (LysM cre IL-4Ra À/lox ) mice were protected from EAE. The protection afforded by IL-4Ra-deficiency was not due to IL-10-, IFN-c-, NO-or IDO-mediated suppression of T-cell responses but was dependent upon the presence of regulatory T cells (Tregs). This investigation highlights the importance of macrophages and Tregs in regulating central nervous system inflammation and demonstrates that macrophages activated in the absence of Th2 cytokines can promote disease suppression by Tregs. Keywords: EAE; macrophage; IL-4Ra; T regulatory cell; immune regulation Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), models aspects of MS including autoimmune Th response development and central nervous system (CNS) inflammation. Mice immunized with myelin proteins or immunodominant peptides of myelin develop an ascending progressive paralysis mediated by CD4 T cells, 1 and migration of these myelin-specific CD4 cells to the CNS induces inflammation, demyelination and axonal/ neuronal damage. 2 Autoreactive CD4 T cells are essential in triggering EAE; however, macrophages are required to facilitate the invasion of the autoreactive T cells into the CNS parenchyma and are thus also essential in the development of autoimmune pathology. 3 Macrophage depletion or deactivation completely blocks the egress of T cells from the perivascular spaces into the parenchyma thus preventing the disease-causing demyelination and tissue damage. 3 Conversely, mice that exhibit greater numbers of activated macrophages have been shown to develop a more rapid onset of EAE. 4 Cytokines produced by Th2 cells (especially IL-4) have been associated with remission from EAE, 5 and the levels of the Th2-associated cytokines, IL-4 and IL-10, are increased within the CNS during recovery from EAE. 6 Moreover, administration of IL-4 or immune deviation to enhance Th2 cell development can reduce or inhibit EAE. 7-9 Using mice deficient in the STAT6 pathway, which controls the differentiation of cells into a Th2 phenotype, a more severe course of EAE develops establishing a regulatory function for Th2 cytokines in vivo during EAE. 10 However, despite the protective effect of Th2 cytokines in EAE and MS, a recent study has shown that IL-4 receptor alpha-deficient (IL-4Ra À/À ) m...

A modified ELISA protocol can be used to for the detection of both drug concentrations and ADA in patients receiving either adalimumab or infliximab. The ELISA incorporates those features identified in the literature as important for the accurate analysis of these antibodies and uses laboratory facilities and reagents that are widely available. It therefore provides a relatively simple and low cost assay for therapeutic drug monitoring of inpatients receiving adalimumab or infliximab.

We evaluated 24 mothers whose babies had congenital hypothyroidism (CH) for the presence of immunoglobulins (Igs) that inhibited [125I]bovine TSH binding and blocked TSH-induced growth and function of FRTL-5 cells. Results were compared with those from 2 mothers with known primary myxedema (atrophic thyroiditis) whose babies had transient CH and with normal controls. Only 1 prospectively evaluated CH mother had potent TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs. Further study of this discordant mother's serum indicated that she was hypothyroid, probably due to atrophic thyroiditis. Both mothers with known primary myxedema had blocking IgGs. The thyroid growth-blocking activity was verified by cell count, could be absorbed by and eluted from Staphylococcal protein-A, indicating that it was an IgG, and was not an anti-TSH idiotype. Half-maximal inhibition was similar in the three different assays for thyroid-blocking activity, suggesting that TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs in some patients with primary myxedema may be the same antibody population. There was no correlation with the titer of antimicrosomal antibodies. These data suggest that maternal thyroid-blocking IgGs interacting with the TSH receptor do not play a role in most cases of sporadic CH. Determination of TSH binding inhibitory IgGs, but not antimicrosomal antibodies, is a sensitive screening test for the presence of TSH receptor-blocking antibodies.

Feline hyperthyroidism bears a strong clinical and pathologic resemblance to toxic nodular goiter in humans. To evaluate whether the observed thyroid growth might be due to circulating thyroid antibodies, as has been postulated in humans, we studied the effect of purified immunoglobulin (Ig) G preparations on a rat thyroid follicular (FRTL-5) cell line. When compared with control, hyperthyroid cat IgG caused significantly increased [3H]-thymidine (Tdr) incorporation into DNA (p less than 0.02) and stimulated cellular proliferation 15-fold. Stimulation of 3H-Tdr incorporation tended to be biphasic and could be inhibited completely by a potent, specific TSH receptor blocking antibody. Hyperthyroid cat IgG also significantly inhibited 125I-bTSH binding to porcine thyroid membranes, an effect that could be reproduced using electrophoretically pure IgG and normal cat thyroid membranes. Unlike its effect on growth, hyperthyroid cat IgG did not stimulate intracellular cAMP, and there was no correlation between thyroid function in vivo and IgG growth-promoting activity in vitro. These data suggest that elevated titers of thyroid growth IgGs, probably acting through the TSH receptor, are present in feline hyperthyroidism and may play a role in goiter formation. Unlike growth, the thyroid hyperfunction observed is not IgG dependent. Further study of feline hyperthyroidism may contribute important insights into human nodular goiter and into the mediation of thyroid growth in general.