Mice of the strain MRL/Mp-lpr/lpr develop a lupus erythematosus-like syndrome that includes the production of autoantibodies specific for nucleic acid-containing cellular components. We have fused spleen cells from such a mouse with the myeloma SP 2/0 and examined the antibodies produced by the resultant cloned hybrid cell lines by using immunoprecipitation and immunofluorescence techniques. Three types of monoclonal antibodies, specific for Sm, DNA, or rRNA, all antigens to which patients who have lupus make antibodies, have been identified. Patient anti-Sm antibody had previously been reported to precipitate five small nuclear ribonucleoproteins that contain U-1, U-2, U-4, U-5, and U-6 RNAs. The monoclonal anti-Sm antibody gives the same immunoprecipitation pattern, providing direct evidence that the Sm antigen resides on all these RNA-protein complexes. Monoclonal anti-Sm antibody will be valuable in deciphering the biological function of these ubiquitous small nuclear RNPs. A simple competition radioimmunoassay using the monoclonal anti-Sm antibody to titer patient sera is also presented. Uses of monoclonal antibodies for the study of autoimmune disease are discussed.The sera of patients and mice that have autoimmune disorders contain antibodies whose presence often results in tissue injury. The mechanisms leading to the development of autoantibodies are not well understood. However, the appearance of specific antibodies in patient sera has been reported to be associated with particular clinical signs of disease (1). Studies with monoclonal antibodies having the same specificity as such autoantibodies could result in a clearer understanding ofboth the mechanisms leading to the formation of autoantibodies and the role of such antibodies in producing disease. Mouse monoclonal antibodies to DNA and ribosomal RNA have been described (2, 3).Autoantibodies also provide potent tools to probe the structure and function ofthe cellular constituents against which they are directed. We have previously used antibodies from the sera of patients who have systemic lupus erythematosus (SLE) to examine the antigens designated Sm, RNP, La, and Ro (4-6). Each of these antigens resides on discrete particles composed of RNA and protein and called either small nuclear ribonucleoproteins (snRNPs) or small cytoplasmic ribonucleoproteins.Anti-Sm has been found to precipitate five different snRNPs, containing the small RNAs U-1, U-2, U-4, U-5, and U-6, from mammalian cell extracts. One snRNP that bears the RNP as well as the Sm determinant appears to be involved in the nuclear splicing of mRNA precursors (7), while cellular roles for the Laand remaining Sm-bearing snRNPs and for the Ro-containing small cytoplasmic RNPs are unknown. The availability of monoclonal antibodies directed against snRNPs would eliminate many uncertainties in experimental interpretation raised by the use of patient sera.Antibodies to Sm are found in certain SLE patients (1), dogs with a lupus-like syndrome (8), and the MRL/Mp-lpr/lpr (MRL/1) and MRL/M...

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Cowhage spicules provide an important model for histamine-independent itch. We determined that the active component of cowhage, termed mucunain, is a novel cysteine protease. We isolated mucunain and demonstrate that both native and recombinant mucunain evoke the same quality of itch in humans. We also show that mucunain is a ligand for protease-activated receptors two and four. These results support and expand the relationship between proteases, protease-activated receptors, and itch.

Leishmaniasis is a protozoan disease whose diverse clinical manifestations are dependent both on the infecting species of Leishmania and on the immune response of the host. Transmission of the disease occurs through the bite of a sand fly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis, limited to the mucous membranes in mucosal leishmaniasis, or spread throughout the reticuloendothelial system in visceral leishmaniasis or kala azar. Three rare clinical variants of cutaneous leishmaniasis include diffuse cutaneous leishmaniasis, leishmaniasis recidivans, and post-kala-azar dermal leishmaniasis.

Itch is a topic to which everyone can relate. The physiological roles of itch are increasingly understood and appreciated. The pathophysiological consequences of itch impact quality of life as much as pain. These dynamics have led to increasingly deep dives into the mechanisms that underlie and contribute to the sensation of itch. When the prior review on the physiology of itching was published in this journal in 1941, itch was a black box of interest to a small number of neuroscientists and dermatologists. Itch is now appreciated as a complex and colorful Rubik’s cube. Acute and chronic itch are being carefully scratched apart and reassembled by puzzle solvers across the biomedical spectrum. New mediators are being identified. Mechanisms blur boundaries of the circuitry that blend neuroscience and immunology. Measures involve psychophysics and behavioral psychology. The efforts associated with these approaches are positively impacting the care of itchy patients. There is now the potential to markedly alleviate chronic itch, a condition that does not end life, but often ruins it. We review the itch field and provide a current understanding of the pathophysiology of itch. Itch is a disease, not only a symptom of disease.