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ID PMID Title PublicationDate abstract
11056762 Relationship between the occurrence of anti-SSA, anti-SSB autoantibodies and HLA class II 2000 Though at present there is no evidence-based algorithm for the treatment of primary Sjögren's syndrome, it is generally accepted that glucocorticosteroid (GS) therapy must be introduced in cases with severe systemic manifestations. As the side-effects of the GSs are well known, it would be useful to know in advance how the patients will respond to this type of treatment. For this reason we measured the in vitro steroid sensitivity of 29 SS patients using inhibition of antibody dependent cellular cytotoxicity (ADCC) test by methylprednisolone compared to that of 28 controls. SS patients proved to be significantly less sensitive to GSs than controls (inhibition of ADCC reaction: 42.4 vs 53.1%; p < 0.01). This was especially true in SS patients with anti-SSA and/or SSB autoantibody positivity and with HLA-DR2 and/or -DR3 alleles. Comparing the results of the in vitro GS sensitivity and the clinical effectiveness of the previously applied corticosteroid therapy it seems that steroid inhibition of ADCC reaction has a predictive value in determination of in vivo sensitivity to GSs. However, in patients with decreased in vitro GS sensitivity a more expressed in vivo steroid sensitivity cannot be excluded.
9867125 Differential cytokine mRNA expression in human labial minor salivary glands in primary Sjà 1998 Cytokines are known to be involved in a number of autoimmune conditions and are increasingly viewed as key components in numerous aspects of normal and abnormal cell functions. The purpose of the present study was to investigate possible immunopathogenic mechanisms within the labial minor salivary glands of patients with primary Sjögren's syndrome (pSS) by examining differential cytokine gene expression in individual cell populations (acini, ducts, or lymphoid cells). A cell-specific microdissection technique in combination with reverse transcription-polymerase chain reaction (RT-PCR) and Southern hybridization using 32P-labeled cytokine gene-specific probes was utilized to measure cytokine messenger RNA expression in individual cell populations of patients and healthy controls. mRNAs for interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta1) were detected in the epithelial cells (acini and ducts) and lymphoid cells of the labial minor salivary glands of pSS patients. The expression levels of these mRNAs in the epithelial cells were either up- or down-regulated by adjacent focal infiltrating lymphoid cells. mRNAs for all of the above cytokines, with the exception of IFN-gamma, were detected in salivary tissues of healthy volunteers. The epithelial cells in the salivary glands are active participants in the autoimmune-mediated process of pSS, as evidenced by their ability to express a high frequency and wide variety of cytokines. The presence of an infiltrating lymphoid focus within the gland appeared to modulate cytokine gene expression by the salivary epithelial cells.
9448184 Multiple pancreatic masses associated with autoimmunity. 1998 Jan A 59-year-old woman was detected to have a high titer of serum gamma-globulin, positive antinuclear antibody and multiple pancreatic masses. In the course of 1 yr, Sjögren's syndrome developed, and her pancreatic masses spread diffusely and compressed the main pancreatic duct. A pancreatic biopsy by an exploration of the abdomen showed that many CD4 positive T-lymphocytes had infiltrated to the ducts and acinar cells expressing HLA-DR antigens. This suggested a diagnosis of autoimmune-related pancreatitis. She was treated with oral prednisolone, and a marked improvement of the above abnormal findings followed. In this report, a case of autoimmune-related multiple pancreatic masses associated with Sjögren's syndrome is presented, and a possible mechanism is discussed.
9068290 Characterisation of follicular dendritic cells in labial salivary glands of patients with 1997 Feb OBJECTIVE: To localise and characterise follicular dendritic cells (FDC) present in autoimmune lesions of primary Sjögren syndrome. METHODS: Cryostat sections of labial salivary glands from 15 patients with primary Sjögren syndrome were examined by an indirect immunoperoxidase technique and monoclonal antibodies to a panel of dendritic cell markers. Tonsils from two controls were also examined for the same markers. RESULTS: FDC were localised in the centre of 75% of lymphoid focal structures in labial salivary glands biopsies. FDC in labial salivary glands of patients with primary Sjögren syndrome expressed CD35, CD11c, and CD106 (VCAM-1) in a pattern similar to FDC in tonsils, but they did not express either CD14 or CD11b. This indicates that they may not be of myeloid origin, while FDC in tonsillar lymphoid follicles strongly expressed both CD14 and CD11b. FDC in labial salivary glands of patients also lacked VLA-2 alpha and VLA-3 alpha, which were expressed by FDC in tonsils. CONCLUSIONS: The characteristic phenotype and origin of these cells may be of importance in the immune responses involved in Sjögren syndrome and the retention of infiltrating lymphocytes in the glands.
10918563 Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic dilemmas in thre 2000 Jul Cowden's syndrome is a multisystem disease inherited as an autosomal dominant trait with incomplete penetrance and variable expression. The disease has typical oral manifestations which often precede more systemic involvement, and the dental professional is therefore well placed to institute a regime of regular checks to ensure early treatment of any neoplasms which may occur. However, since not all of the classical signs are present in all patients, diagnosis may be difficult. The case report of a patient with most of the features of Cowden's syndrome is presented and features compared with two other possible cases.
10846400 [Sjögren's syndrome with malignant lymphoma, interstitial pneumonia, and pulmonary hypert 2000 Mar A 62-year-old woman was admitted to our hospital for further examination of cough and dyspnea on exertion. She had suffered xerostomia and xerophthalmia for 7 years. Physical examinations showed purpura on the lower extremities, Raynaud's phenomenon, and swelling of the parotid glands. Laboratory data disclosed thrombocytopenia, hypergammaglobulinemia, and high titers of anti-nuclear antibody, anti SS-A, and anti SS-B antibodies. Sicca symptoms, a positive Schirmer's tear test, and laboratory findings together yielded a diagnosis of Sjögren's syndrome. Chest X-P and computed tomographic films demonstrated diffuse reticulonodular shadows and multiple nodules in the left lower lung. Echocardiography and right cardiac catheterization revealed enlargement of the right ventricle, tricuspid regurgitation, and elevated pulmonary arterial pressure. Histologic findings from an open-lung biopsy specimen revealed accumulation of inflammatory cells and fibrosis around broncho-vascular bundles, and diffuse large cell lymphoma. Despite a favorable response to chemotherapy, the patient died of right ventricular failure.
10434857 Treatment of dry eye by autologous serum application in Sjögren's syndrome. 1999 Apr AIM: To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjögren's syndrome. METHODS: The stability of essential components (EGF, vitamin A, and TGF-beta) in preserved serum were examined following preservation at 4 degrees C and -20 degrees C. In a primary clinical trial, 12 patients with Sjögren's syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro. RESULTS: EGF, vitamin A, and TGF-beta were well preserved for up to 1 month in the refrigerator at 4 degrees C and up to 3 months in the freezer at -20 degrees C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface. CONCLUSION: Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjögren's syndrome.
9598887 A double blind placebo controlled trial of azathioprine in the treatment of primary Sjögr 1998 May OBJECTIVE: To establish whether there is a place for low dose azathioprine (AZA) as a disease modifying agent in patients with uncomplicated primary Sjögren's syndrome (SS). METHODS: Twenty-five patients with primary SS were entered into a double blind, placebo controlled trial of AZA (1 mg/kg/day) for a period of 6 months. RESULTS: Six patients, all receiving active drug, withdrew because of side effects. There was no significant change in disease activity variables when measured clinically, serologically, or histologically. CONCLUSION: This trial suggests that low dose AZA does not have a role as a disease modifying agent in SS.
9324013 Sensitivity and positive predictive value of Medicare Part B physician claims for rheumato 1997 Sep OBJECTIVE: To examine the sensitivity and positive predictive value of Medicare physician claims for select rheumatic conditions managed in rheumatology specialty practices. METHODS: Eight rheumatologists in 3 states abstracted 378 patient office records to obtain information on diagnosis and office procedures. The Medicare Part B physician claims for these patient visits were obtained from the Health Care Financing Administration. The sensitivity of the claims data for a specific diagnosis was calculated as the proportion of all patients whose office records for a particular visit documented that diagnosis and who also had physician claims for that visit which identified that diagnosis. The positive predictive value was evaluated in a separate sample of 331 patient visits identified in Medicare physician claims. The positive predictive value of the claims data for a specific diagnosis was calculated as the proportion of patients with that diagnosis coded in the claims for a particular visit who also had the diagnosis documented in the medical record for that visit. RESULTS: Ninety percent of abstracted office medical records were matched successfully with Medicare physician claims. The sensitivity of the Medicare physician claims was 0.90 (95% confidence interval [CI] 0.85-0.95) for rheumatoid arthritis (RA), 0.85 (95% CI 0.73-0.97) for systemic lupus erythematosus (SLE), and 0.85 (95% CI 0.78-1.0) for aspiration or injection procedures. The sensitivity for osteoarthritis (OA) of the hip or knee was < or = 0.50 if 5-digit codes specifying anatomic site were required. The sensitivity for fibromyalgia (FM) was 0.48 (95% CI 0.28-0.68). The positive predictive values were at least 0.90 for RA, SLE, and aspiration or injection procedures. Positive predictive values for FM and the 5-digit site-specific codes for OA of the knee were 0.83 (95% CI 0.66-1.0) and 0.88 (95% CI 0.75-1.0), respectively, while the positive predictive value of the 5-digit site-specific codes for OA of the hip was zero (95% CI 0-0.26). The positive predictive value of OA at any site was 0.83 (95% CI 0.76-0.90). CONCLUSION: In specialty practice, Medicare physician claims had high sensitivity and positive predictive value for RA, SLE, OA without specification of anatomic site, and injection or aspiration procedures. The claims had lower sensitivity and predictive value for FM and for OA of the hip. The accuracy of Medicare physician claims for other conditions and in the primary care setting requires further investigation.
11247877 Calcium pyrophosphatase dihydrate (CPPD) crystal deposition disease in a teaching hospital 2001 Apr OBJECTIVE: A Medline electronic search showed a paucity of reports on calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) from the Gulf region. To date only a single case report has been published from this region. Therefore, this study aimed, firstly, at finding out the prevalence of chondrocalcinosis in adult Arabs in Kuwait presenting with knee arthritis and, secondly, at carrying out an observational study of CPPD-CDD among Arabs in Kuwait. METHODS: For the study of the prevalence of chondrocalcinosis 100 consecutive adult patients presenting with knee arthritis were radiologically examined. For the observational study the clinical, laboratory, and radiological findings were analysed in patients with CPPD-CDD seen over a period of five years. RESULTS: This study showed the presence of chondrocalcinosis in two (2%) of the 100 adult Kuwaiti and other Middle-Eastern Arab patients (70 men, 30 women, median age 50 (range 45-80)) who presented to the rheumatology clinic for the evaluation of knee pain. When the younger age of the group (only three patients aged >70) is taken into account the figure was comparable with that reported from Western countries. Over a period of five years a total of 2726 new patients were evaluated at the rheumatology clinic of this institution. A diagnosis of crystal arthritis was made in 85 patients (3%). Fourteen of these 85 (that is, 16.5%, but 0.5% of the total cases) were diagnosed with definite (eight patients) or probable (six patients) CPPD-CDD. Different clinical presentations, including that of acute monarthritis (that is, pseudogout), premature generalised osteoarthritis, and polyarticular rheumatoid-like presentations, were seen in different patients. Overlap with true gout, with the additional presence of monosodium urate crystals in the joint aspirate, was seen in two patients. CONCLUSION: The present report shows that CPPD-CDD may not be uncommon among Arabs in the Gulf region. A high degree of clinical awareness and routine examination of joint aspirates with careful analysis for crystals may make it a more common diagnosis in this part of the world. In this regard it is interesting to note that cases and case series including familial cases have been reported from North Africa, especially Tunisia, indicating that the disease has been well described in Arabs of other geographical regions.
11698484 Possible role of organ-specific autoantigen for Fas ligand-mediated activation-induced cel 2001 Nov 15 Activation-induced cell death (AICD) is a well-known mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). In this study, we demonstrate that the administration of a soluble form of anti-FasL Ab, FLIM58, results in severe destructive autoimmune exocrinopathy in the murine model of human Sjögren's syndrome (SS), and we found that an organ-specific autoantigen may play an important role on down-modulation of AICD. A high titer of serum autoantibodies against 120-kDa alpha-fodrin autoantigen was detected in the FLIM58-treated mice, and splenic T cell culture supernatants contained high levels of IFN-gamma. In vitro T cell apoptosis assay indicated that FasL-mediated AICD is down-regulated by autoantigen stimulation in spleen cells from the murine SS model, but not from Fas-deficient MRL/lpr mice and FasL-deficient MRL/gld mice. FasL undergo metalloproteinase-mediated proteolytic processing in their extracellular domains, resulting in the release of soluble trimeric ligands (soluble FasL). We showed that the processing of soluble FasL occurs in autoantigen-specific CD4(+) T cells, and that a significant increase in expressions of metalloproteinase-9 mRNA was observed in spleen cells from SS model mice. These findings indicate that the increased generation of soluble FasL inhibits the normal AICD process, leading to the proliferation of effector CD4(+) T cells in the murine SS model.
11035437 Increased serum soluble CD14, ICAM-1 and E-selectin correlate with disease activity and pr 2000 To improve monitoring of immunological and disease activity, we determined soluble markers of activity of the monocyte/macrophage system (sCD14) and the vascular endothelium (sE-selectin, sICAM-1) in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) in comparison to patients with infections or sepsis. Concentrations of sCD14, sICAM-1 and sE-selectin (soluble CD14, ICAM-1 and E-selectin, respectively) were measured in serum samples from patients with SLE and pSS, patients with sepsis, different infectious diseases and healthy controls using ELISA systems. Elevated levels of sE-selectin and sICAM-1 were detected in patients with SLE as well as sepsis, in contrast to patients with a localized infection (SLE and sepsis, respectively, versus infection P<0.001; Kruskal-Wallis test). Levels of sCD14 were persistently elevated in sera from patients with SLE, whereas these values decreased rapidly after effective therapy in patients with sepsis or infection. A continuous elevation of all of these three parameters was associated with a fatal outcome in patients with sepsis as well as in patients with SLE. Combined elevation of sCD14, sICAM-1 and sE-selectin correlates with the prognosis in patients with active SLE and indicates a remarkable immune activation involving the monocyte/macrophage system and the endothelium comparable to an activation found only in patients with sepsis.
9872481 Cryoglobulinemia in primary Sjögren's syndrome: prevalence and clinical characteristics i 1998 Dec OBJECTIVES: To determine the prevalence and nature of cryoglobulins in a large series of patients with primary Sjögren's syndrome (SS) and identify the clinical and immunologic features related to their presence. METHODS: In a cross-sectional study, we investigated 115 consecutive patients (107 women and eight men) with primary SS. All patients fulfilled four or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993. Serum cryoglobulinemia was measured in all patients. Serum samples were obtained at 37 degrees C, and cryoglobulinemia was estimated by centrifugation after incubation at 4 degrees C for 7 days. The type of cryoglobulinemia was identified by agarose gel electrophoresis and immunofixation. RESULTS: Cryoglobulins were detected in the sera of 18 (16%) of our patients with primary SS; most were IgMkappa monoclonal/IgG polyclonal. When compared with patients without cryoglobulins, those with cryoglobulins presented a higher prevalence of leukocytoclastic cutaneous vasculitis (56% v8%, P < .001), hypocomplementemia (75% v 2%; P < 0.001) and antibodies to hepatitis C virus (HCV) (47% v8%, P < .001). Liver involvement (clinical signs, biochemical features, or ultrasound/histological data of liver disease) was present in all patients (100%) with cryoglobulins and HCV infection but in only 11% of patients with cryoglobulins without HCV infection (P < .001). CONCLUSIONS: Leukocytoclastic cutaneous vasculitis, hypocomplementemia, and HCV infection are associated with the presence of cryoglobulins in the sera of patients with primary SS. Testing for HCV infection is recommended for patients with SS and cryoglobulinemia because of its high prevalence and its strong association with liver disease.
9486406 cDNA cloning of a novel autoantigen targeted by a minor subset of anti-centromere antibodi 1998 Feb Using autoimmune serum from a patient with anti-centromere antibodies, we have identified and partially characterized a novel protein with a mol. wt of approximately 27 kD (hereafter referred to as p27). A cDNA expression library was screened with this serum, and two overlapping inserts were isolated among three positive clones other than clones corresponding to centromere protein (CENP)-B and CENP-C. Analysis of the sequence showed an open reading frame of approximately 0.6 kb encoding 199 amino acids with a predicted mol. wt of 21.5 kD. Immunoblotting analysis with bacterial recombinant p27 showed that approximately 2% of anti-centromere antibody-positive patients had autoantibodies to p27, whereas only one of 215 autoimmune patients without anti-centromere antibodies reacted with the recombinant. All five cases with anti-p27 antibodies, who were diagnosed as having scleroderma and/or Sjögren's syndrome, showed internal organ involvement. Although affinity-purified anti-p27 human or mouse polyclonal antibodies failed to stain any cellular structures in an immunofluorescence study, the potential association of anti-p27 with anti-centromere antibodies suggests that this novel autoantigen might play a role in mitosis.
11491495 Undifferentiated connective tissue disease with antibodies to Ro/SSa: clinical features an 2001 Jul OBJECTIVE: To evaluate the clinical and serologic profile, the rate of progression to well defined CTD and the possible predictors of disease evolution in patients affected by UCTD with antibodies anti-RoISSA. METHODS: 148 patients diagnosed as UCTD were retrospectively evaluated. Antibodies to SSA/Ro were determined by counter-immunoelectrophoresis and ELISA. RESULTS: Thirty-six patients (24.3%) developed a well-defined CTD after a mean follow-up of 4.5 years. Most patients developed primary Sjögren's syndrome (SS) (50%) or systemic lupus erythematosus (SLE) (30.5%). Leukopenia and xerophthalmia developed more frequently in the group of patients evolving to defined CTDs (p < 0.0032 and p < 0.0063). Leukopenia independently predicted the evolution in CTD by multivariate regression analysis (p < 0.019). Anti-dsDNA predicted the evolution in SLE (p < 0.0207), while the presence of additional anti-ENA specificity to anti-Ro/SSA was not associated with the outcome. CONCLUSION: 24.3% of patients with UCTD and antibodies to Ro/SSA can progress in a relatively short period of time to well-defined CTDs. The development of primary SS could be predicted by xerophthalmia and SLE by the appearance of anti-dsDNA antibodies.
10972902 Mechanisms of neonatal tolerance induced in an animal model for primary Sjögren's syndrom 2000 Sep Neonatal exposure to autoantigen is believed to induce effective antigen-specific T-cell tolerance in experimental models of autoimmunity. We have identified 120 kDa alpha-fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen-specific T-cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down-regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1-mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti-120 kDa alpha-fodrin response in vivo, by tolerization of the autoantigen-reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.
10736099 Diminished expression of CD59 on activated CD8+ T cells undergoing apoptosis in systemic l 2000 Mar The present study was undertaken to examine the phenotype of T cells undergoing in vitro apoptosis in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). Compared with normal controls, we found diminished expression of CD59 antigen (one of the cell-surface complement-regulatory proteins) on CD8+ T cells, but not on CD4+ T cells, from patients with SLE and SS. Three-colour immunofluorescence analysis revealed that these CD59dim CD8+ T cells were activated T cells, expressing both human leucocyte antigen (HLA)-DR and CD45RO antigens. In addition, these CD59dim CD8+ T cells were more susceptible to in vitro apoptosis than CD59bright CD8+ T cells. In two patients with active lupus, the percentage of CD59dim CD8+ T cells was significantly decreased after steroid therapy. These findings suggest that decreased expression of CD59 antigen on in vivo-activated CD8+ T cells may be correlated with disease activity and may be involved in activation-induced apoptosis in patients with SLE and SS.
10555043 Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in 1999 Nov OBJECTIVE: To clone and characterize human anti-Ro/SSA autoantibodies from a patient with primary Sjögren's syndrome (pSS). METHODS: Monoclonal antibodies (mAb) were raised from the peripheral blood of a patient with pSS using Epstein-Barr virus transformation and a hybridoma technique. Specificity was determined using cell extracts, recombinant Ro 52-kd, Ro 60-kd, and La proteins as well as Ro 52-kd peptides in enzyme-linked immunosorbent assay (ELISA) and Western blot. The immunofluorescence pattern was analyzed using cultured human and mouse cell lines. Complementary DNA was amplified by polymerase chain reaction, and Ig variable (V)-region genes were directly sequenced. RESULTS: Two human anti-Ro 52-kd mAb of IgM isotype, denoted SG1 and SG3, were cloned from the peripheral blood of a patient with pSS. The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot. SG1 reacted specifically with 1 peptide, amino acids 136-156, of the Ro 52-kd protein, and SG3 was mapped to react with a recombinant fragment representing amino acids 136-292. Immunofluorescence studies revealed cytoplasmic staining with both mAb. Both were encoded by V(H)3-family genes. SG1 was highly homologous to the DP-77 germ-line gene, with 2 replacement mutations and 1 silent. It utilized the DPL-11 germ-line gene from the Vlambda2-family gene, with 1 silent mutation. SG3 was 100% homologous to the DP-47 germ-line gene, combined with a Vkappa1-family gene that was 100% homologous to the A30 germ-line gene. CONCLUSION: Two human mAb were demonstrated to be specific for the Ro 52-kd protein and to be directed against 2 different epitopes, 1 linear and 1 conformation-dependent, within a region previously described to be immunodominant. Somatic hypermutation appeared to be of minor importance in generating these 2 specificities.
10335942 Lymphoepithelial duct lesions in Sjögren-type sialadenitis. 1999 Apr It is not clear, whether the so-called basal cells of the salivary striated ducts are an independent cell-type distinct from myoepithelial cells, making characterization of the cell proliferation typical of the duct lesions in Sjögren-type sialadenitis/benign lymphoepithelial lesion (BLEL) difficult. An immunohistochemical investigation including different cytokeratin subtypes, alpha-actin, Ki-67 and Bcl-2 was directed at the epithelial cytoskeleton in normal parotid parenchyma (n=8), BLEL (n=12), HIV-associated lymphoepithelial cysts (n=8) and palatine tonsils (n=8). There are profound morphological and functional differences between basal and myoepithelial cells in the normal salivary duct. Development of duct lesions in BLEL arises from basal cell hyperplasia of striated ducts with aberrant differentiation into a multi-layered and reticulated epithelium, characterized by profound alteration of the cytokeratin pattern. This functionally inferior, metaplastic epithelium is similar to the lymphoepithelial crypt epithelium of palatine tonsils. The often postulated participation of myoepithelial cells in duct lesions of Sjögren disease/BLEL cannot be supported. We regard the designations lymphoepithelial lesion and lymphoepithelial metaplasia as the most appropriate.
9636185 Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoant 1998 Jun 23 The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulin-dependent diabetes and Sjögren's syndrome. NOD.Igmu null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Igmu null mice fail to lose secretory function as determined by stimulation of the muscarinic/cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab')2 fragments from parental NOD mice or human primary Sjögren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [3H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren's syndrome.