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ID PMID Title PublicationDate abstract
7515243 A heterogeneous immune response to an SmD-like epitope by SLE patients. 1994 Feb Two mouse cDNA clones were isolated by immunoscreening with an SLE serum. These clones encode an epitope which consists of a di-peptide repeat (Gly-Arg)n (n = 9 and 19 in isolated clones). These sequences, when expressed as fusion proteins, inhibit the binding of antibodies from one patient's serum to the SmD autoantigen. This cross-reactivity is based on the sequence identity with the carboxyterminal end of the human SmD [(Gly-Arg)g]. An Exonuclease III deletion analysis demonstrates that the minimal number of Gly-Arg repeats necessary for immune recognition on the Western blot is patient-specific, and varies from nine to three. The defined epitope is recognized by 35% of sera from patients with SLE as well as with other autoimmune diseases (rheumatoid arthritis, scleroderma, Sjogren's syndrome), in contrast to SLE-specificity of anti-Sm antibodies. Affinity-purified antibodies of the identified epitope cross-react with EBNA1 protein in EBV-infected B-cell lines.
8216415 The structure of aggrecan fragments in human synovial fluid. Evidence that aggrecanase med 1993 Sep OBJECTIVE: To determine the proteolytic fragmentation patterns and N-terminal sequence of aggrecan fragments in human synovial fluid from patients with inflammatory arthritides, joint injury, or osteoarthritis (OA). METHODS: Knee synovial fluid was obtained from patients with joint injury, OA, acute pyrophosphate arthritis (pseudogout), reactive arthritis, psoriatic arthritis, or juvenile rheumatoid arthritis. Chondroitin sulfate-substituted aggrecan fragments present in the fluid were purified by cesium chloride gradient centrifugation and enzymatically deglycosylated. Core protein species were determined by N-terminal analysis and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with electroblotting and detection with monoclonal antibody 3B3. RESULTS: Samples from patients with joint injury, OA, and inflammatory joint disease all showed a similar 3-band pattern, with core sizes of approximately 200 kd, 170 kd, and 135 kd. In all samples, diffuse immunoreactive products were also seen, with an apparent size of > 250 kd. N-terminal analysis of core preparations of all samples showed a consistent single predominant sequence, beginning at alanine 374 of the human aggrecan core protein. CONCLUSION: The aggrecan fragments present in joint fluids from patients with various inflammatory arthritides, joint injury, or OA result from a predominant cleavage of the human aggrecan core protein at the glutamate 373-alanine 374 bond within the interglobular domain, between the G1 and G2 domains. The consistent pattern of fragments seen on SDS-PAGE and the single predominant N-terminal sequence suggest a common degradative mechanism of aggrecan in these different joint conditions. The identity of the proteolytic agent (aggrecanase), however, remains unknown. These results appear to have important implications with regard to the development of therapies to protect cartilage from degradation in patients with joint disease.
9363178 Pulmonary involvement in primary Sjögren's syndrome. 1996 Sep Interstitial pulmonary fibrosis and tracheobronchial sicca are the most common presentation of pulmonary involvement in primary Sjögren's syndrome. There is wide spectrum of less common manifestations, including pulmonary arterial hypertension, pseudolymphoma, pulmonary lymphoma, lymphocytic interstitial pneumonitis, amyloidosis, and pleurisy. Pulmonary function test abnormalities showing a restrictive pattern and cellular abnormalities in bronchoalveolar lavage fluid for prevalent in patients without respiratory complaints and normal chest radiographs. Long-term prospective controlled studies are needed to determine the clinical course and significance of these findings.
8679304 Epitope specificity of anti-HIV antibodies in human and murine autoimmune diseases. 1996 Apr 10 This article reports the HIV epitope specificity of antibodies present in the sera of HIV-negative patients with autoimmune diseases. Recombinant gp120 and a panel of synthetic peptides derived from the amino acid consensus sequences of either related (gp120, gp41, and p24) or unrelated (Mage-1, necdin, heat shock protein [65 kDa], and amyloid) HIV proteins were tested by a specific ELISA. The first set of experiments performed on four patients with Sjögren's syndrome (SjS) and four patients with systemic lupus erythematosus (SLE) revealed a significant anti-gp120 antibody reactivity in autoimmune patients when compared to healthy HIV-negative controls. Moreover, such binding could be almost completely inhibited by preincubation with free gp120. A significant anti-p24 reactivity was observed in 18 of 29 sera from SjS patients and in 13 of 25 sera from SLE patients, while anti-gp41 was observed only in 3 of 14 SjS and in 2 of 20 SLE-affected patients. Similar analyses were performed in the murine model of autoimmunity, showing that sera from MRL/lpr mice were able to bind all HIV-related peptides in an age-dependent manner. The analysis of a panel of HIV-unrelated peptides showed that SLE as well as MRL/lpr sera bind both HIV-related and unrelated peptides, while SjS sera failed to do so, revealing the polyclonal nature of the SLE and MRL/lpr repertoire and the oligoclonal reactivity of SjS sera. This is also supported by inhibition experiments, which showed that SLE, but not SjS, sera competitively inhibited the binding to HIV gp120 peptide of sera from autoimmune MRL/lpr mice. These results indicate that an overlapping polyclonal repertoire is present in both SLE and MRL/lpr sera, while the oligoclonal specificity of SjS antibodies may be related to a specific, nonpolyclonal, activation against putative retroviral antigens.
8340232 Molecular analysis of HLA class II genes in primary Sjögren's syndrome. A study of Israel 1993 Apr In an attempt to define the role of HLA class II genes in predisposition to primary Sjögren's syndrome, patients of two different ethnic groups (Israeli Jews and Greeks of non-Jewish origin) suffering from this disorder were studied. Oligonucleotide genotyping revealed the majority in both groups to carry either DRB1*1101 or DRB1*1104, alleles that are in linkage disequilibrium with DQB1*0301 and DQA1*0501. The high frequency of the two alleles in these SS patients is in contrast with the accepted association of primary SS with HLA-DR3 in Italian and American individuals. Molecular analysis of DQB1 and DQA1 alleles found in American Caucasian and American black SS (or SLE) patients demonstrated high frequencies of DQB1*0201 and DQA1*0501. The fact that the majority of SS patients, across racial and ethnic boundaries, carry a common allele, DQA1*0501, implies its involvement in the predisposition to primary SS. Based on sequence analysis and the computer imaging of the HLA class II molecule structure, a hypothetical model for the role of the DQ molecule in promoting primary SS is proposed.
8639178 Cellular adhesion molecules in rat adjuvant arthritis. 1996 May OBJECTIVE: To examine adhesion molecule expression during the progression of inflammation in a rheumatoid arthritis model of adjuvant-induced arthritis (AIA) in rats. METHODS: Immunohistochemical analysis was used to determine the distribution of the following adhesion molecules: lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18), Mac-1 and p150/95 (CD11bc/CD18), intercellular adhesion molecule 1 (ICAM-1), and CD44 in tissue sections from the ankle joints of rats with AIA. Control animals and those with AIA were killed at intervals over a 54-day period after injection with mineral oil and Mycobacterium butyricum, respectively. RESULTS: CD44 and LFA-1 were expressed on lymphocytes, macrophages, and synovial (ST) lining cells. CD44 expression on macrophages was found to be increased compared with control animals by day 18, and was significantly increased by day 41. CD44 expression on lymphocytes significantly increased earlier, on days 11-18. Increased LFA-1 expression on macrophages occurred late, on day 41. LFA-1 expression on lymphocytes was significantly increased on days 25, 47, and 54. ST lining cells exhibited two distinct periods of increased expression, one early, on days 11-25 and one later, on days 41-54. CD11b/c was expressed on macrophages and ST lining cells, showing a significant increase on AIA rat ST lining cells compared with control animals on day 4. No differences in ICAM-1 expression on endothelial cells between rats with AIA and controls were found on any of the days examined. CONCLUSION: CD44 expression is up-regulated on macrophages and lymphocytes during the early development of AIA, while LFA-1 expression is up-regulated later in the development of AIA. The up-regulation of CD44 and LFA-1 at different times in the development of AIA suggests an important role for these adhesion molecules in establishing and sustaining an inflammatory response in the AIA joint.
1387597 Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome 1992 Sep The low affinity IgE receptor Fc epsilon RII (CD23) is important in several aspects of T and B cell function. In this study serum levels of soluble CD23 (sCD23) were measured in three groups: 26 female patients with systemic lupus erythematosus (SLE), 21 females with primary Sjögren's syndrome (pSS) and 25 normal healthy females. The concentration of sCD23 was determined using an enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased levels of sCD23 were observed in pSS and in SLE patients compared with controls (median 23.0 versus 8.6, P less than 0.0002 and 18.1 versus 8.6, P less than 0.002 respectively). While the median level of sCD23 was found to be higher in pSS than in SLE the difference was not statistically significant. Patients with SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23 than patients not on this treatment (median 28.9 versus 14.4, P less than 0.05). Amongst the control patients sCD23 was inexplicably lower in the female members relative to the males (median 8.5 versus 12.3, P less than 0.05). Although serum IgG and IgA levels were significantly elevated in pSS and SLE patients relative to controls there was no direct correlation between sCD23 and the serum levels of these immunoglobulins. We conclude that B cell hyperactivity which occurs in both pSS and SLE is associated with raised levels of sCD23.
7781436 A role for chronic hepatitis C virus infection in a patient with cutaneous vasculitis, cry 1995 Jun A six-year history of repeated attacks of fatigue, fever, arthralgias, skin changes, Raynaud's phenomenon, and neuropathy is reported in a patient with chronic liver disease. The following diagnoses were made: (1) leukocytoclastic vasculitis; (2) acute urticaria; (3) cryoglobulinemia type II with Raynaud's phenomenon and low serum level of C4; (4) peripheral polyneuropathy; (5) sicca syndrome; and (6) chronic hepatitis C virus infection. Despite therapy with corticosteroids symptoms increased gradually over years. In the first PCR of the nested PCR analysis, HCV-RNA was exclusively detected in the cryoglobulin fraction but not in the serum supernatant, suggesting that antibodies bind HCV particles, forming circulating immune complexes. As diagnoses 1-5 are well-known organ manifestations of cryoglobulinemia, we speculated whether treatment of hepatitis C with IFN-alpha (3 million IU IFN-alpha 2b three times a week) would inhibit HCV replication, decrease the cryocrit level and thereby ameliorate organ manifestations such as neuropathy and vasculitis. During treatment with IFN-alpha only a very weak or no signal could be detected for HCV-RNA in the cryoglobulin fraction as well as in the serum supernatant. This held true also for the serum supernatant in the second PCR. In parallel, cryoglobulin level, immunoglobulins, and liver enzymes decreased substantially to normal or near normal levels. Clinical symptoms-leukocytoclastic vasculitis and neuropathy-disappeared. We conclude that chronic HCV infection is involved in the pathogenesis of cryoglobulinemia and that IFN-alpha might be an effective treatment in these patients.
8737717 CD4 cytopenia and occasional expansion of CD4+CD8+lymphocytes in Sjögren's syndrome. 1996 Mar OBJECTIVES: To define whether Sjögren's syndrome (SS) patients have lymphocytopenia compared to healthy controls, and to assess which lymphocyte subset might be involved. The presence of any concurrent infection was recorded. METHODS: A cohort of ten consecutive patients with SS was studied, and the results were compared with ten sex- and age-matched controls (C). RESULTS: In SS, a significant cytopenia of CD4+ (679 +/- 339 vs 1110 +/- 222 cells/mm3, p < 0.005) and an even more impressive decrease in the CD4+CD45 RA+ (242 +/- 154 vs 491 +/- 190 cells/mm3, p < 0.005) subset was observed. An absolute CD4 lymphocytopenia (CD4+ < 300 cells/mm3) was seen in two patients. In one patient an unusual finding was the expansion of a double positive population of CD4+CD8+ lymphocytes. No striking relationship with any particular infection was shown. A retrospective review of the absolute CD4+ cytopenia in 54 consecutive SS cases revealed a prevalence of 5.5%. CONCLUSION: Some SS patients have T lymphocytopenia which mainly affects the CD4+CD45 RA+ subset. Occasional cases with absolute CD4 lymphocytopenia may also be observed. These patients show some evidence of mild recurrent or chronic, but never severe, opportunistic infections.
7485204 Autoimmune thyroid disease in primary Sjögren's syndrome. 1995 Nov PURPOSE: To evaluate the prevalence of autoimmune thyroid disease and thyroid dysfunction in patients with primary Sjögren's syndrome. PATIENTS AND METHODS: Thyroid function of 33 patients with primary Sjögren's syndrome was clinically and biochemically evaluated. Thyroid hormones and autoantibodies against thyroid peroxidase, thyroglobulin, and thyroid hormones were measured. RESULTS: Autoimmune thyroid disease and thyroid dysfunction were found in 15 cases (45%): autoimmune thyroiditis in 8 (24%); autoimmune hyperthyroidism in 2 (6%); and reversible iodine-induced hypothyroidism in the remaining 5 (15%). One or more of the evaluated autoantibodies were detected in 8 euthyroid patients (24%). Overall, the prevalence of autoantibodies against thyroid peroxidase, thyroglobulin, thyroxine, and triiodothyronine was 45%, 18%, 42%, and 36%, respectively. CONCLUSIONS: The high prevalence of autoimmune thyroid disease and thyroid dysfunction found in primary Sjögren's syndrome, using sensitive immunologic and thyroid function tests, suggest that both diseases are more frequently associated than it was previously thought, and should be sought clinically and by laboratory tests in all patients with primary Sjögren's syndrome.
7934493 Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome. 1994 Oct 22 There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögren's syndrome in endemic areas.
8049546 Clinical, serological and immunogenetic features of Japanese anti-Ro/SS-A-positive patient 1994 Sixteen anti-Ro/SS-A-positive patients with recurrent annular erythema, which has recently been recognized as a unique cutaneous manifestation of Sjögren's syndrome, were studied. Eight of the 16 patients met the American Rheumatism Association criteria for systemic lupus erythematosus. Fifteen patients had anti-La/SS-B antibodies. Antibodies against U1RNP were detected in 2 patients with systemic lupus erythematosus, 1 with anti-Sm antibodies. Patterns of autoimmune response to Ro/SS-A antigens were variable by immunoblot analysis. HLA typing by the standard complement-dependent microcytotoxicity assay revealed that all the 16 patients were positive for HLA-DRw52 antigens but negative for either HLA-B8 or HLA-DR3 which is reportedly associated with the autoimmune response to Ro/SS-A antigens in white and black patients.
8468491 Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary 1993 Apr 15 To better define the genetic factors that predispose to primary Sjögren's syndrome (SS), we have used polymerase chain reaction in combination with oligonucleotide probe hybridization and DNA sequencing to analyze HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles in Caucasoid (California), Japanese (Tokyo), and Chinese (Shanghai and Beijing) SS patients. In comparison to local controls in each region, we found: 1) increased frequency of the predicted haplotype HLA-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 in Caucasoid patients (p < 0.001); 2) increased frequency of the predicted haplotype HLA-DRB1*0405-DRB4*0101-DQA1*0301-DQB1*0401 in Japanese patients (p < 0.05); 3) increased frequency of the predicted haplotype DRB1*0803-DQA1*0103-DQB1*0601 in Chinese patients (p < 0.05); and 4) no statistically significant association with DPB1 alleles in any group, although an increased number of Caucasoid and Japanese SS patients possessed DPB1*0301. Comparison of DNA sequences for the three disease-associated haplotypes in these ethnic groups revealed a shared region of predicted amino acids from positions 58 to 69 in the first domain of HLA-DQB1. These results extend previous studies by demonstrating that no single class II allele was associated with 1 degree SS in the different ethnic groups. However, a shared amino acid motif in the DQB1 first domain was present in each disease-associated haplotype.
1486744 The diagnostic value of salivary fluid levels of beta 2-microglobulin, lysozyme and lactof 1992 Dec In search of a simple non-invasive diagnostic test for primary Sjögren's syndrome (SS) the concentration of beta 2-microglobulin (beta 2-m), lysozyme (LZM) and lactoferrin (Lf) was measured in stimulated parotid saliva of 39 patients with primary SS, 42 patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) and in 41 normal control individuals. Salivary fluid levels of beta 2-m, LZM and Lf exceeding the mean + 2 x standard deviation of healthy control values were found in respectively 58%, 23%, and 26% of the primary SS patients and in 7%, 11% and 0% of the NON-SS patients. The results of this study indicate that due to the low sensitivity the tests are not suitable as a screening procedure for patients suspected of having primary SS. However, measurement of beta 2-m in stimulated parotid saliva may be used as an adjunctive diagnostic test for primary SS.
1285893 Diffuse infiltrative lymphocytosis syndrome in children and adults infected with HIV-1: a 1992 Oct Certain maternal/infant pairs, as well as other high-risk adults, develop a host-response HIV-1 infection characterized by circulating and tissue infiltrative CD8 T-cell lymphocytosis, termed Diffuse Infiltrative Lymphocytosis Syndrome (DILS). DILS primarily occurs in the salivary glands, lungs, renal interstitium, and gastrointestinal tract. DILS differs from Sjogren's syndrome in the degree of salivary gland enlargement, high frequency of extraglandular manifestations, paucity of autoantibodies, and distinct immunogenetic associations. Salivary gland B-cell lymphoma is a complication common to both conditions. The circulating CD8 T cells in DILS have a memory phenotype. Egress into target tissues involves adhesion molecule receptor-ligand interactions, apparently in response to the local presence of HIV-1. Immunogenetic predisposition involves interaction between both MHC classes I and II loci. This disease appears to reflect a specific host response that leads to persistence of monocyte-tropic, rather than T-cell-tropic, HIV-1 strains, in an analogous fashion to Visna Maedi virus disease in sheep. The development of DILS in children appears to be regulated in a dominant fashion by maternally or paternally inherited MHC class II alleles in response to transplacentally or perinatally acquired maternal HIV-1 strains.
1388639 Use of a molecularly cloned human SS.B antigen to detect anti-SS.B antibodies. 1992 Jun The aim of this study was to examine the utility of diagnostic assays based on recombinant SS.B/La (rSS.B). Using this antigen, we have developed an ELISA and an immunoblot and compared these recombinant antigen-based assays with traditional thymus extract-based counterimmunoelectrophoresis (CIEP). Using the recombinant ELISA, the incidence of anti-SS.B in 184 normal blood donors was 2.2% (four sera). These four sera were all low titre, i.e., 3-5 SD above the mean. Of 38 sera positive for anti-SS.B by CIEP, 37 were positive in both recombinant assays (97.4% concordance). Anti-SS.B titre in CIEP correlated strongly with results of the rSS.B-based ELISA, but the ELISA was 3,000-fold more sensitive. In an analysis of 152 autoimmune sera containing anti-DNA, anti-RNP, anti-centromere, anti-SS.A/Ro or anti-cardiolipin, all of which were negative for anti-SS.B/La by CIEP, the recombinant assays detected 17 new anti-SS.B positives. These positive results were found only in sera which had previously been characterised by CIEP as anti-SS.A/Ro positive. Anti-SS.B/La antibodies detected by recombinant SS.B assays were found to be highly predictive of primary Sjögren's syndrome. Our results show that rSS.B can have an important role in the design of sensitive and specific assays for anti-SS.B. The diagnostic significance of anti-SS.B/La as a guide to primary Sjögren's syndrome is not diminished by the increased sensitivity of recombinant SS.B assays.
7799367 Arthritis in a patient with psoriasis after interferon-alpha therapy for chronic hepatitis 1994 Sep A 27-year-old man with psoriasis was administered with leukocyte derived interferon-alpha for the treatment of chronic persistent hepatitis C. After 3 weeks of injections and eventual normalization of serum levels of alanine aminotransferase, he began to experience polyarthritis, with worsening of psoriatic skin lesions. Tests for antinuclear antibodies and rheumatoid factor were negative, indicating a direct association between interferon therapy and occurrence of seronegative arthritis.
8950841 The role of gut inflammation in the pathogenesis of spondyloarthropathies. 1996 The concept of spondyloarthropathy (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteriae, and since the gut is implicated in different forms of spondyloarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondyloarthropathies by performing ileocolonoscopies. In the first ileocolonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly without any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileocolonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileocolonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondyloarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileocolonoscoped patients were reviewed 2 to 9 years later: about 6% of SpA patients not presenting any sign of Crohn's disease at first investigation but demonstrating gut inflammation on biopsy, developed full-blown Crohn's disease. The discovery of subclinical gut inflammation in the SpA had therapeutic consequences. Sulphasalazine (SASP) has been proven to be an active drug in the treatment of IBD. Since the gut could play a crucial role in SpA, it was logic to use this drug in the treatment of this disease. Multiple open and double-blind studies have proven the effectiveness of this drug in SpA; recent studies concluded that the beneficial effect of the drug in this disease entity is more prominent on the peripheral arthritis than on the axial disease.
8709903 [Follow-up and immunologic findings in drug-induced myasthenia]. 1996 May 15 PATIENT AND METHOD: We report 5 patients, who developed myasthenia, four of them after treatment on D-penicillamine, one after treatment on chloroquine. 3 patients suffered from rheumatoid arthritis, one from a psoriatic arthritis and one from cirrhosis of the liver. Three patients developed an ocular myasthenia, one patient an oculopharyngeal and one patient has had generalized myasthenic syndrome. RESULTS: Four patients showed an improvement of clinical status within days up to 18 months following discontinuation of the therapy, whereas one patient deteriorated. The quickest improvement was observed in the patient with chloroquine induced myasthenia. Four patients had raised acetylcholine-receptor antibody titers. The patient with chloroquine induced myasthenia had had a normal acetylcholin-receptor antibody titer. The human leucocyte antigen type was compared with the results of literature. CONCLUSION: To what extent human leucocyte antigen type HLA DR 4 has a correlation with the development of myasthenia following treatment on chloroquine can not yet be answered with respect to the very small number of cases at the moment.
8278823 Mechanism of action of hydroxychloroquine as an antirheumatic drug. 1993 Oct The antimalarial agents chloroquine and hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These compounds lead to improvement of clinical and laboratory parameters, but their slow onset of action distinguishes them from glucocorticoids and nonsteroidal antiinflammatory agents. Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus. It is proposed that the antirheumatic properties of these compounds results from their interference with "antigen processing" in macrophages and other antigen-presenting cells. Acidic cytoplasmic compartments are required for the antigenic protein to be digested and for the peptides to assemble with the alpha and beta chains of MHC class II proteins. As a result, antimalarials diminish the formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and result in down-regulation of the immune response against autoantigenic peptides. Because this mechanism differs from other antirheumatic drugs, antimalarials are well suited to complement these other compounds in combination drug therapy.