Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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10961261 | Threats to chronically ill adolescents. Challenges for physicians as we approach the next | 1998 Feb | The frequency of all forms of juvenile arthritis, including juvenile rheumatoid arthritis, other major connective tissue diseases, and other rheumatic diagnoses, is estimated to be approximately 160,000-190,000 U.S. children under 15 years of age. The author suggests that the legitimization of alternative medicine and the corporatization of U.S. health care are undermining the quality of care that chronically ill adolescents receive. | |
9262263 | An hypothesis on the association between maternal smoking and dizygotic twinning. | 1997 Jul | There is good evidence that smoking is a marker for high steroid hormone concentrations (at least at the time that smoking is initiated). This would explain the finding that smoking is associated with dizygotic, though not monozygotic, twinning. The notion that smoking and other elective behaviours (e.g. drinking alcohol, opting for vasectomy and use of oral contraception) are markers or indices of high hormone concentrations may have widespread repercussions for cross-sectional epidemiological studies of such risk factors for diseases thought to be partially caused by high (e.g. prostatic and breast cancers) or low (e.g. rheumatoid arthritis) concentrations of these hormones. | |
10513798 | Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles. | 1999 Sep | OBJECTIVE: To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes. METHODS: We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories. RESULTS: Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect. CONCLUSION: These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease. | |
9217364 | [Inhibitory effects of portal venous injection of type II collagen in collagen-induced art | 1997 Jun | Collagen-induced arthritis (CIA) is useful animal model for human rheumatoid arthritis. We investigated the inhibitory effects of portal venous (p.v.) injection of type II collagen (CII) in CIA. The arthritis was suppressed by p.v. injection of CII before immunization for CIA induction. The p.v. route was more effective than intravenous or intragastric routes in the induction of tolerance in CIA. The dose of CII necessary for CIA suppression was 10 micrograms/20 g body weight in p.v. injection. Both anti-CII IgG and anti-CII IgG 2 a levels in serum were reduced in mice injected CII before induction of CIA. However, anti-CII IgG 1 levels did not differ between mice injected with CII and mice injected with buffer alone. Thus, the specific reduction in anti-CII IgG 2 a levels in mice treated by p.v. injection before immunization suggests that the suppression of CIA could be responsible for hypofunction of Th 1 cells. Reduction of anti-CII IgG and suppression of arthritis were observed when CII was injected through portal vein after immunization for CIA as well. | |
11360405 | Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subje | 2001 Feb | BACKGROUND: To evaluate T helper 1 (Th1)/Th2 cells and cytokines in patients with three different subtypes of juvenile rheumatoid arthritis (JRA). METHODS: Peripheral blood was obtained from 25 children with JRA suffering from active arthritis (8 systemic, 9 pauciarticular and 8 polyarticular). Eight healthy children were recruited as controls. T helper cells from peripheral blood mononuclear cells (PBMC) were evaluated by using intracellular staining analysis of cytokine production with 3-colored flow cytometry. A Th1 cell was defined as an interferon-gamma (IFN-gamma) producing CD4+ cell, and a Th2 cell as an interleukin-4 (IL-4) producing CD4+ cell. The production of IL-2, IL-4, IL-5 and IFN-gamma from PBMC was measured by ELISA. RESULTS: In comparison with normal controls, the patients with JRA had significantly fewer Th2 cells among their PBMC (0.78 +/- 0.56% vs. 5.44 +/- 2.33%, p < 0.001). The percentage of Th1 cells among PBMC was not different between patients and normal controls (4.32 +/- 3.24% vs. 4.52 +/- 2.56%, p > 0.5). The ratio of Th1/Th2 cells in the patient group was significantly higher than the control group (8.38 +/- 8.63 vs. 0.95 +/- 0.66, p < 0.001). After 24-hour culture, the PBMC from JRA patients produced less IL-4 than that of controls (3.61 +/- 0.56 pg/mL vs. 4.29 +/- 0.68 pg/mL, p = 0.002). The production of IL-2, IL-5, and IFN-gamma did not show significant differences between JRA patients and normal controls. CONCLUSION: Decreased IL-4 producing T-helper cells were identified in all three subtypes of JRA. This implicates that an imbalance of Th sub-populations might be a predominant factor in JRA pathogenesis. | |
9585926 | [Surgical procedures in the cervical spine in polyarthritis. Indications and surgical stra | 1998 Mar | Patients with rheumatoid arthritis suffer frequently from instabilities and deformities of the cervical spine which require surgical treatment. The most frequent indication for surgery represents the transverse atlantoaxial instability. As long the atlantoaxial instability remains reducible in extension a limited posterior exposure and screw fixation is adequate. Only situations with fixed dislocations and signs of myelopathy require anterior transoral decompression with simultaneous occipitocervical fusion. In the lower cervical spine, kyphotic deformities require anterior decompression and posterior stabilization in the case of electrophysiologically confirmed neurological deficits. A combined procedure with anterior vertebrectomy and decompression and posterior plate fixation is indicated since the poor bone quality rarely allows anterior stable fixation. | |
11416778 | Kidney disease and arthritis in a cohort study of workers exposed to silica. | 2001 Jul | Silica exposure has been associated with kidney disease and rheumatoid arthritis; an autoimmune mechanism has been proposed. Approximately 2 million people are occupationally exposed to silica in the United States, 100,000 at more than twice the National Institute for Occupational Safety and Health recommended exposure limit of 0.05 mg/m(3). We examined renal disease morbidity and mortality, as well as arthritis mortality, in a cohort of 4,626 silica-exposed workers in the industrial sand industry (an industry previously unstudied). We compared the cohort with the U.S. population and also conducted internal exposure-response analyses using a job-exposure matrix based on more than 4,000 industrial hygiene samples. We found excess mortality from acute renal disease [standardized mortality ratio (SMR) = 2.61, 95% confidence intervals (95% CIs) = 1.49--4.24; 16 deaths], chronic renal disease (SMR = 1.61, 95% CI = 1.13--2.22; 36 deaths), and arthritis (SMR = 4.36, 95% CI = 2.76--6.54; 23 deaths) on the basis of multiple-cause mortality data, which considered any mention of disease on a death certificate. Linking the cohort with the U.S. registry of end-stage renal disease for the years 1977-1996, we found an excess of end-stage renal disease incidence (standardized incidence ratio = 1.97, 95% CI = 1.25--2.96; 23 cases), which was highest for glomerulonephritis (standardized incidence ratio = 3.85, 95% CI = 1.55--7.93; 7 cases). We found increasing end-stage renal disease incidence with increasing cumulative exposure; standardized rate ratios by quartile of cumulative exposure were 1.00, 3.09, 5.22, and 7.79. A positive exposure-response trend was also observed for rheumatoid arthritis on the basis of death certificate data. These data represent the largest number of kidney disease cases analyzed to date in a cohort with well-defined silica exposure and suggest a causal link between silica and kidney disease. Excess risk of end-stage renal disease due to a lifetime of occupational exposure at currently recommended limits is estimated to be 14%, above a background end-stage renal disease risk of 2%. | |
9150088 | Long-term health outcomes and quality of life in American and Italian inception cohorts of | 1997 May | OBJECTIVE: To determine whether demographic, clinical, and immunogenetic variables measurable during the first 6 months of illness long-term health outcomes and quality of life in patients with juvenile rheumatoid arthritis (JRA). METHODS: Patient eligibility criteria: (1) first examined in our units between 1958 and 1990 within 6 months of onset of symptoms; (2) diagnosis of JRA by American College of Rheumatology criteria; (3) disease duration of at least 5 years at the time of assessment of outcome. Instruments used: (1) the Health Assessment Questionnaire (HAQ, short form), or Childhood HAQ (CHAQ) to measure disability (0-3 scale), (2) pain, and (3) parental assessment of overall well being, each scored on a 15 cm visual analog scale; (4) the Quality of Life Scales (QOLS) (adults only). Independent variables that showed significant results using univariate tests underwent multiple logistic regression analysis. RESULTS: 227 patients were available for analysis. Mean duration of disease at time of assessment of outcome was 15 years (range 5.3-36.1). Univariate tests allowed 11 variables for disability, 9 for pain, 7 for overall well being, and 4 for QOL into the multivariate analysis. The best predictor of higher disability was the articular severity score (odds ratio, OR, 5.69) while antinuclear antibody positivity foretold less disability (OR 0.29). HLA-DR5 positivity conferred the greatest risk for pain (OR 3.34), while HLA-B5, DR3, and C3 were protective (OR 0.25, 0.28, 0.33, respectively). Early hand involvement was the strongest predictor of poorer overall well being (OR 8.75). Only the erythrocyte sedimentation rate was predictive of future QOL, but the model yielded a low C statistic (< 70%) and the OR 95% confidence limits were extreme (OR 9.77; 95% confidence interval, 1.22-77.8). CONCLUSION: Clinical and immunogenetic variables measurable within 6 months of onset of JRA can be used to predict future disability, pain, and well being. QOL appears more difficult to forecast, perhaps due to the multiple domains that make up this outcome. Further study is needed to identify other genetic and laboratory factors that predict outcome in JRA with greater precision. | |
11327252 | Clinical and immunological characteristics of elderly onset Sjögren's syndrome: a compari | 2001 Apr | OBJECTIVE: To compare the clinical and laboratory characteristics of patients with primary Sjögren's syndrome (SS) with an elderly onset to those with a younger onset. METHODS: The study group comprised 85 consecutive patients (79 women and 6 men) attending the Sjögren's clinic. Primary SS was diagnosed according to the San Diego criteria. Elderly onset disease (EOD) was determined as the appearance of symptoms suggestive of SS after age 65. Clinical and laboratory variables for EOD were compared to those of a younger onset disease (YOD). Salivary and serum samples of all patients were examined for concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA). RESULTS: Seventeen patients with SS (20%) matched the definition of EOD and their median disease onset was 71 years (range 65-80). No significant differences were noted in the clinical disease manifestations between the 2 groups of patients. Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6 and HA levels were detected in the YOD group compared to the EOD group with SS (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml, respectively) (p < 0.0001). CONCLUSION: EOD SS has somewhat milder clinical symptoms with fewer immunological manifestations than YOD. The elevations of salivary IL-6 and HA in the younger group of SS patients support in part the differences in the inflammatory process between the 2 groups. | |
9708505 | Regional cerebral blood flow and glucose metabolism in Sjögren's syndrome. | 1998 Aug | Involvement of the brain is one of the most important complications of Sjögren's syndrome (SS). However, diagnosis of brain involvement in SS patients is difficult due to the lack of effective imaging methods. In this study, we compared two updated brain imaging modalities, 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET and 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT, in SS patients with neuropsychiatric manifestations, to detect glucose metabolism of the brain and regional cerebral blood flow. METHODS: Sixteen primary female SS patients with normal brain MRI findings were enrolled in this study. RESULTS: Technetium-99m-HMPAO SPECT findings were abnormal in 13 (81%) patients. Parietal and temporal lobes were the most common areas of brain involvement. Fluorine-18-FDG PET findings were abnormal in 3 (19%) patients. Temporal lobes were the most common areas of brain involvement. CONCLUSION: We conclude that brain HMPAO SPECT has better correlation with clinical manifestations than brain FDG PET or CT/MRI. | |
9670336 | Ankylosing spondylitis with primary Sjögren's syndrome: the first two case-reports. | 1998 Jun | Sjögren's syndrome and ankylosing spondylitis can occur either alone or in conjunction with other disorders. We report on two patients who met criteria for both primary Sjögren's syndrome and ankylosing spondylitis. Class I and II histocompatibility phenotypes were strikingly similar in the two patients and are in favor of a chance association. | |
9599316 | Autoantibodies in salivary hypofunction in the NOD mouse. | 1998 Apr 15 | The nonobese diabetic (NOD) mouse exhibits spontaneous salivary gland infiltration and loss of salivary function independent of its propensity to develop diabetes, and thus can serve as a model for salivary hypofunction in Sjögren's syndrome (SS). Studies by others have indicated that this pathology depends on lymphocytes and thus may be autoimmune mediated. We have found that NOD mice four months of age and older exhibit a 90-95% reduction in pilocarpine-stimulated salivary flow (5.8 +/- 6.6 mg/5 min) as compared to age- and sex-matched C57B1/10 controls (98.4 +/- 52.3 mg/5 min). These mice simultaneously possess only sparse mononuclear cell infiltrates (averaging approximately one small and one large focus per whole-gland section) in the submandibular glands, suggesting that loss of salivary function does not require massive infiltration of the salivary glands. NOD serum autoantibodies to salivary gland proteins are demonstrable by Western blotting, and, as in a subset of SS patients, some NOD serum autoantibodies recognize neural antigens. Splenic T-cell reactivity to salivary and neural proteins can also be observed. Transfer experiments using NOD mouse serum suggest that loss of salivary function, evaluated as a decrease in pilocarpine-stimulated flow rate, can be transferred by humoral factors, possibly autoantibodies. These results suggest that autoimmune mechanisms dependent on both autoantibody and autoreactive T cells can mediate loss of salivary function, and that salivary and/or neural antigens may serve as a target for these autoimmune reactions. | |
9492444 | Riehl's melanosis-like eruption associated with Sjögren's syndrome. | 1997 Dec | A 58-year-old Japanese female complained of facial erythema and Riehl's melanosis-like pigmentation. Histological examination showed liquefaction degeneration of the basal cells and pigment incontinence. Direct immunofluorescence revealed no deposition of immunoglobulins or complements at the basement membrane zone. Patch test and photopatch test using cosmetics and detergents she had been using were negative. She was diagnosed with Sjögren's syndrome based upon dryness of the mouth, dense periductal infiltration of lymphocytes and plasma cells in the labial salivary gland, positive Shirmer's test, hyper-gamma-globulinemia, positive antinuclear antibody, and positive anti-SSA (Ro) antibody. The pigmentation gradually faded away when she protected her face from ultraviolet irradiation while continuing use of the cosmetics and detergents. Riehl's melanosis-like eruption could be a cutaneous manifestation of Sjögren's syndrome closely related with anti-SSA (Ro) antibody. | |
9365094 | In vitro induction of proinflammatory cytokine secretion by juvenile rheumatoid arthritis | 1997 Nov | OBJECTIVE: To characterize juvenile rheumatoid arthritis synovial fluid (SF) immune complexes and to examine their interaction with leukocytes. METHODS: SF immunoglobulin-containing fractions were prepared by sequential chromatography on protein A and Sephacryl 300. Fractions were subdivided according to molecular weight, characterized for immunoglobulin and complement content, and incubated with either promonocytic U937 cells or normal human peripheral blood mononuclear cells (PBMC). RESULTS: High molecular weight SF immunoglobulin-containing fractions stimulated the release of interleukin-1beta (IL-1beta) from U937 cells. These same complexes stimulated tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) from PBMC. Lower molecular weight material was less efficient in inducing any of the cytokines. TNFalpha and IL-1beta were the earliest of the messenger RNAs examined to be induced by the high molecular weight complexes. However, the secretion of IL-6, IL-8, and GM-CSF stimulated by the complexes was not completely dependent upon the secretion of IL-1beta. Addition of IL-1 receptor antagonist to the cell cultures reduced GM-CSF and IL-6 production by 40% and IL-8 production by 25% in PBMC. CONCLUSION: SF immunoglobulin fractions contain immune complexes that vary in size, composition, and phlogistic potential. High molecular weight complexes are capable of inducing a spectrum of proinflammatory cytokines, all of which have been implicated in the pathogenesis of rheumatic disease. | |
11026060 | [Sjögren's syndrome and multiple myeloma]. | 2000 Sep 17 | In our recent work we present two cases of coexisting Sjögren's syndrome and myeloma multiplex. Our results obtained studying a high number of patients suggest that the occurrence of myeloma in Sjögren's syndrome is much higher than in normal population. This can possibly be explained by the common pathogenetical factors of the two diseases. The survival of one of our two patients in 4 years, and her disease is still in complete remission. The possible explanation of the therapeutical success can be the rather aggressive chemotherapeutical approach in her case. Perhaps the prognosis of myeloma coexisting with Sjögren's syndrome is different that of pure myeloma, it is suggested that the earliest possible aggressive therapy of myeloma accompanied by Sjögren's syndrome can be useful and recommendable. | |
10628930 | Efficacy of low-dose prednisolone maintenance for saliva production and serological abnorm | 1999 Dec | OBJECTIVE: To evaluate efficacy of low dose prednisolone maintenance in patients with primary Sjögren's syndrome. METHODS: An open, prospective pilot study of prednisolone for the treatment of 20 patients with primary Sjögren's syndrome was performed. Evaluations included the amount of whole saliva measured by the Saxon test, serological abnormalities and oral symptoms. RESULTS: Initial dosage of prednisolone was 15.0+/-1.5 (mean+/-SEM) mg/day. Maintenance dosage was 7.5-5.0 mg/day. Follow-up period was 26.3+/-3.8 months (range 3-48). The amount of whole saliva significantly increased after 1 month of prednisolone therapy and the increase continued up to 48 months by maintaining low-dose prednisolone. A mean percent increase of whole saliva from baseline ranged from +105.2+/-36.2% to +245.7+/-82.1%. Serum IgG, anti-SS-A/Ro, anti-SS-B/La antibodies and IgM rheumatoid factor levels significantly decreased throughout the study with partial decreases of IgA and IgM levels. The improvement of subjective oral symptoms was also confirmed. CONCLUSION: Low-dose prednisolone maintenance may have a worthwhile clinical benefit in patients with primary Sjögren's syndrome that deserves further evaluation in a controlled trial. | |
9058667 | Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis. | 1997 Mar | OBJECTIVE: To evaluate the diagnostic significance of antineutrophil cytoplasmic antibodies (ANCA) by assessing the prevalence of ANCA in juvenile chronic arthritis (JCA) (n = 93) of either oligoarticular, polyarticular, or systemic onset. To investigate the prevalence of ANCA in other diseases of childhood characterized by chronic inflammation (n = 44), such as cystic fibrosis, juvenile diabetes mellitus, and connective tissue diseases. METHODS: Indirect immunofluorescence on both ethanol and paraformaldehyde fixed neutrophils, ELISA for specific antigens, Western blotting using sonicated neutrophils. RESULTS: ANCA were detected in the sera from 35% of patients with JCA, and in only 7% of patients with other inflammatory diseases. Regarding the onset type of JCA, ANCA were present in 44% of patients with oligoarticular onset, in 36% with polyarticular onset, and in 16% with systemic onset. All but one ANCA positive serum sample produced a perinuclear fluorescence pattern on ethanol fixed granulocytes. However, on neutrophils fixed with paraformaldehyde either a cytoplasmic (14%) or a nuclear (23%) staining pattern was observed, suggesting that both cytoplasmic and nuclear autoantibodies occur in JCA. Further characterization studies showed that ANCA in JCA are not directed against proteinase 3, elastase, or myeloperoxidase. On Western blots ANCA in JCA incidentally showed reactivity with either lactoferrin (5%) or 2 polypeptides of 66/67 kDa (9%). CONCLUSION: Prevalence and antigenic specificity of ANCA in JCA are clearly different from adult onset rheumatoid arthritis or other juvenile chronic inflammatory disorders. | |
17984887 | Procedure for rehabilitation of the knee following synovectomy in patients with rheumatoid | 2000 Dec 30 | At the Poznań Rheumatology Center in Srema synovectomy of the knee joint is one of the treatment methods applied in cases where "rheumatoid granules" occur in the knee, or in recurrent exudative infections. One of the essential elements of therapy is to begin post-operative rehabilitation with active exercises as soon as 48 hours after surgery. This method is used to eliminate adhesions in the operating field and achieve a full range of movement in the joint without the need to apply painful and injurious redressing of the joint. The procedure used with the patient after surgery and the choice of kinesitherapeutic methods is the result of many years of experience. Post-operative procedures are concluded within 2-3 weeks when the range of movement achieved in the joint is greater than or equal to pre-operative. | |
11196514 | Clinicopathological findings consistent with primary Sjögren's syndrome in a subset of pa | 2001 Jan | OBJECTIVE: Some patients diagnosed with chronic fatigue syndrome (CFS) have symptoms commonly observed in Sjögren's syndrome (SS), particularly xerophthalmia and xerostomia, leading to speculation that some patients with CFS might have primary SS or that the 2 disorders share common pathophysiological features. We investigated the prevalence of symptoms of mucosal dryness, salivary gland pathology, lacrimal hyposecretion, and autoantibodies (antinuclear antibody, SSA/SSB) among patients diagnosed with CFS. METHODS: Twenty-five subjects with CFS and 18 healthy control subjects were interviewed and examined, had a Schirmer test and fluorescein tear dilution, and underwent minor salivary gland (MSG) biopsy. Antibody to nuclear antigen as well as anti-La (SSA) and anti-Ro (SSB) antibody were available for subjects with CFS. Pathologists unaware of the subject group assignment examined labial salivary gland biopsy specimens and calculated a standard MSG score for each specimen. RESULTS: Mucosal dryness was reported by 13/25 (52%) subjects with CFS, of which 8 (32%) also had MSG score, low Schirmer test value, and symptoms consistent with primary SS (p = 0.05). No control subject met diagnostic criteria for primary SS. MSG focus scores < or =1 were common among both groups (CFS 14/25; controls 15/18). MSG results without pathological alteration were rare, seen in only one control and no CFS patients. Low Schirmer values were found in 10/25 (40%) CFS patients and 1/18 (6%) control (p = 0.01). CONCLUSION: A subset of patients with CFS may have primary SS. | |
10780673 | Two different types of sialoadenitis in the NOD- and MRL/lpr mouse models for Sjögren's s | 2000 Apr | Sjögren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjögren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/Ipr mouse, can be used as models for Sjögren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/Ipr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/Ipr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/Ipr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjögren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. |