muramidase and Spondylitis--Ankylosing

HLA class I molecules play a central role in the immune system by presenting peptide antigens to cytotoxic T cells. Although most HLA class I molecules are associated with β2-microglobulin, HLA class I heavy chain that is not associated with β2-microglobulin is also expressed on certain cells. We recently found that cellular misfolded proteins are transported to the cell surface by HLA class II molecules via association with their peptide-binding grooves. Furthermore, misfolded self-antigens bound to autoimmune disease-susceptible HLA class II molecules are the targets for autoantibodies produced in certain autoimmune diseases. In the present study, we found that misfolded proteins were also transported to the cell surface by specific HLA class I molecules including HLA-B27, which is strongly associated with ankylosing spondylitis. In addition, the efficiency with which HLA class I molecules encoded by each allele transport misfolded proteins to the cell surface was significantly correlated with HLA class I free heavy chain expression on that surface. Moreover, misfolded proteins were coprecipitated with HLA class I free heavy chain but not with correctly folded HLA class I molecules. These findings reveal a novel function of HLA class I molecules to transport misfolded proteins to the cell surface, which might help us to understand the pathogenesis of HLA class I-associated diseases.

Topics: Animals; beta 2-Microglobulin; Chickens; HEK293 Cells; HLA-B27 Antigen; Humans; Muramidase; Protein Folding; Protein Transport; Proteostasis; Proteostasis Deficiencies; Spondylitis, Ankylosing

Increased serum levels of angiotensin converting enzyme and lysozyme are considered as inflammatory markers for diagnosis of sarcoidosis which is an autoimmune inflammatory disease. The purpose of this study is to evaluate the significance of differences in serum angiotensin converting enzyme and lysozyme levels of patients with ocular involvement of other autoimmune inflammatory and infectious diseases.. This is a prospective study involving patients with ankylosing spondylitis, behcet's disease, presumed sarcoidosis, presumed latent tuberculosis, presumed latent syphilis, and control group. The serum levels of angiotensin converting enzyme and lysozyme were analyzed by enzyme-linked immunosorbent assay. Bonnferoni analysis was used to assess pairwise comparisons between the groups.. There was a significant increase in serum angiotensin converting enzyme level in patients with presumed sarcoidosis compared to ankylosing spondylitis (p = 0.0001), behcet's disease (p = 0.0001), presumed latent tuberculosis (p = 0.0001), presumed latent syphilis (p = 0.0001), and control group (p = 0.0001). The increase in serum lysozyme level was significant for patients with presumed sarcoidosis with respect to ankylosing spondylitis (p = 0.0001), behcet's disease, (p = 0.0001) presumed latent tuberculosis (p = 0.001), presumed latent syphilis (p = 0.033), and control group (p = 0.0001).. Elevated serum angiotensin converting enzyme levels are significant for patients with presumed sarcoidosis compared to ocular involvement of other autoimmune diseases such as behcet's disease and ankylosing spondylitis, and ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. However, elevated serum lysozyme level might be also detected in ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis.. NCT02627209. Date of registration: 12/09/2015.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Behcet Syndrome; Child; Communicable Diseases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Latent Tuberculosis; Male; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Prospective Studies; Sarcoidosis; Spondylitis, Ankylosing; Syphilis

Metallothioneins (MTs) are low-molecular-weight cytosolic proteins, which are thought to participate in metal homeostasis and protection against metal toxicity and oxidative stress. MT synthesis can be induced by a variety of inflammatory mediators and antirheumatic drugs, and high levels of MT have been implicated in resistance of cells to some antirheumatic drugs. We studied the expression and localization of MT in synovial tissue samples from patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or osteoarthritis (OA) by quantitative immunohistochemistry. Immunostaining for MT was detected in a large number of intimal lining cells in most of the investigated synovial tissue samples (75%). In a smaller proportion of samples (42%), some of the fibroblast-like cells of the subsynovial layer were also MT positive. Immunostaining and double-staining experiments with antibodies against monocyte-, macrophage- and leucocyte-associated antigens suggested that most of the MT-positive cells were intimal fibroblast-like cells and subsynovial fibroblasts. However, there were no statistically significant differences in the intensity of staining for MT between the rheumatic diseases and OA at the single-cell level. Thus, MT is expressed in synovial tissue and may participate in homeostatic and protective functions. The interindividual variability in the expression of MT in synovial tissue may be related to the therapeutic efficacy of the gold compounds and chemotherapeutic antirheumatic drugs sequestered by MT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Child; Female; Humans; Immunohistochemistry; Joint Diseases; Male; Membrane Glycoproteins; Metallothionein; Mice; Middle Aged; Muramidase; Osteoarthritis; Spondylitis, Ankylosing; Synovial Membrane

Topics: Adult; Antimicrobial Cationic Peptides; Blood Bactericidal Activity; Blood Proteins; Complement System Proteins; Female; Humans; Immunoglobulins; Male; Middle Aged; Muramidase; Properdin; Proteins; Spondylitis, Ankylosing; T-Lymphocytes

Topics: Acid Phosphatase; Alkaline Phosphatase; Aminopeptidases; Arthritis; Cartilage; Cathepsins; Fructose-Bisphosphate Aldolase; Glutathione Reductase; Humans; Joints; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Malate Dehydrogenase; Muramidase; Pyruvate Kinase; Spondylitis, Ankylosing; Synovial Fluid