Autoimmune Rheumatologic Diseases Research Articles

The safety of mycophenolate mofetil in pregnancy

Mycophenolate mofetil (MMF) has proved to be a major addition to the therapeutic options for the treatment of multisystem autoimmune disorders. The majority of the autoimmune rheumatological diseases are more prevalent in women and they are often first diagnosed during childbearing age. MMF use during pregnancy is associated with an increased risk of malformations and first-trimester pregnancy loss. The most frequent malformations include external ear and other facial malformations such as cleft palate and lip. Therefore MMF should be avoided during pregnancy and safe contraceptive methods provided.

NEUROLOGIC COMPLICATIONS OF SJÖGREN SYNDROME AND RHEUMATOID ARTHRITIS

ABSTRACTSjogren syndrome and rheumatoid arthritis are common autoimmune rheumatologic diseases that can be associated with neurologic complications, which can sometimes be the presenting manifestation of the systemic disease. Sjogren syndrome can be associated with prominent peripheral nervous syste

Quinine sulfate inhibits invasion of some bacterial skin pathogens

As some of the many patients who receive antimalarials for the treatment of noninfective inflammatory diseases (lupus erythematosus, collagen vascular diseases, rheumatoid arthritis, and others) are also immunosuppressed because of their disease and/or treatments, and may have concomitant bacterial infections, we investigated the effect of these drugs on the growth and invasion of several bacteria that are commonly associated with skin and soft tissue infections to determine whether they could protect against such conditions and obviate the need for an additional antibiotic drug. The effect of quinine sulfate (QS) at concentrations of 50 and 100 microm on the entry process of Enterobacter agglomerans, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae into Caco-2 cells was studied during the infection period. The invasive efficiency was expressed as the number of viable internalized bacteria obtained by counting the colony-forming units (CFUs). The invasive ability of E. agglomerans and S. aureus was significantly inhibited by 50 and 100 microm QS in a dose-dependent manner when the drug was added to Caco-2 cell monolayers during the infection period; however, QS had no significant effect on the internalization of P. aeruginosa or K. pneumoniae. Antimalarial drugs are currently widely used to treat patients with autoimmune dermatologic and rheumatologic diseases, and have also been recently proposed as additional therapy for patients with human immunodeficiency virus (HIV) infection. These patients, who are often immunocompromised, may receive a secondary advantage from these antimalarials, which may provide some protection against staphylococci (amongst the most important human pathogens causing many superficial and systemic infections) and E. agglomerans.

Stroke-Complicated Endocarditis with Positive Lupus Anticoagulant

Twenty to 40% of patients with infective endocarditis (IE) suffer from neurologic complications. Also many and various markers of immunologic activation have been reported in patients with IE and no history of autoimmune or other rheumatologic diseases. The authors present a case of a patient suffering from IE complicated with major cerebrovascular event with concomitant appearance of lupus anticoagulant (LAC). After successful antibiotic treatment there was major clinical improvement with disappearance of LAC. LAC could be added to the list of immunologic markers appearing in the course of infective endocarditis.

Genetic analysis of a La homolog in Drosophila melanogaster.

People afflicted with certain rheumatological auto-immune diseases produce autoantibodies directed against a select group of proteins such as the La auto-antigen. Biochemical studies have revealed La to be a promiscuous RNA-binding protein that appears to play a role in a variety of intracellular activities such as processing and/or transport of RNA polymerase III precursor transcripts and translational regulation from internal ribosome entry sites (IRES). We have previously identified an RNA-binding protein that is a Drosophila melanogaster homolog of La (D-La) and shown that early transcript accumulation throughout the embryo is later refined to be most prevalent in the visceral mesoderm, gut, gonads and salivary glands. Here we report the first in vivo genetic characterization of a La homolog in a multicellular eukaryote. Lethality was observed in homozygous larvae harboring a small chromosomal deletion that removed the D-La gene, which was rescued by an inducible D-La cDNA transgene. This implies that D-La confers essential functions for larval development. In addition, loss of D-La function gives rise to defects in embryonic midgut morphogenesis; one of the midgut defects correlates with loss of Ultrabithorax ( Ubx ) expression along the second midgut constriction. Finally, genetic interactions between chromosomal deficiencies that remove D-La and certain Ubx alleles were demonstrated in adults. Our results support the hypothesis that D-La provides essential functions for proper Drosophila development and imply that the conserved La family of proteins may perform critical developmental functions in higher eukaryotes.

Immune ablation and stem-cell therapy in autoimmune disease: Immunological reconstitution after high-dose immunosuppression and haematopoietic stem-cell transplantation

Studies on immunological reconstitution after immune ablation and stem-cell therapy may yield important clues to our understanding of the pathogenesis of human autoimmune disease, due to the profound effects of function and organization of the immune system. Such studies are also indispensable when linking clinical sequelae such as opportunistic infections to the state of immune deficiency that ensues after the treatment. Much has been learnt on these issues from comparable studies in haemato-oncological diseases, although it remains to be proven that the data obtained from these studies can be extrapolated to rheumatological autoimmune diseases. Preliminary results from pilot studies in various rheumatological conditions not only pointed to clinical efficacy of the new treatment modality but also unveiled marked effects on T-cell receptor repertoires of circulating T lymphocytes, on titres of autoantibodies and T- and B-cell subsets.