Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 10322570 | Quantitative salivary gland scintigraphy. | 1999 Mar | OBJECTIVE: Uptake of 99mTc-pertechnetate in salivary glands reflects intact salivary gland parenchyma. However, no standardized protocol for an accurate quantification of parenchymal function has been established so far. METHODS: In this paper we report on a validated acquisition protocol supplying a normal database for standardized quantitative salivary gland scintigraphy. RESULTS: The major advantage of salivary gland scintigraphy, as compared to other imaging modalities, is that both parenchymal function and excretion fraction of all four major salivary glands (i.e., parotid and submandibular glands) can be simultaneously quantified with a single intravenous injection. CONCLUSION: Quantitative salivary gland scintigraphy is demonstrated to be a suitable imaging modality for research applications in evaluating the effects of radioprotective drugs on salivary glands. Salivary gland scintigraphy is easy to perform, reproducible and well-tolerated by the patient. | |
| 9608665 | HTLV-I associated sicca syndrome in Guadeloupe: lack of relation with a peculiar encoding | 1998 | We previously reported a strikingly high prevalence of ocular diseases in HTLV-I infected patients in Guadeloupe (Caribbean basin). We sequenced the surface envelope encoding region of 7 HTLV-I proviruses from guadeloupean patients (5 with sicca syndrome, 2 with TSP/HAM). No relation between sequence and disease was observed. These 7 sequences are the first described from Guadeloupe. | |
| 9115907 | Diseases associated with dermatitis herpetiformis. | 1997 Mar | We have studied the occurrence of associated diseases in a cohort of 305 patients with dermatitis herpetiformis (DH) followed up for a mean of 10 years. The results were compared with those from 383 patients with coeliac disease (CD). Twenty-nine (9.5%) patients with DH and 73 (19.1%) with CD had concomitant endocrine or connective tissue disorders. The following associations were found: auto-immune thyroid disease (4.3% of DH patients and 6.0% of CD patients), insulin dependent diabetes (1.0% DH and 5.5% CD), lupus erythematosus (1.3% DH and 0.3% CD), Sjögren's syndrome (1.0% DH and 2.9% CD), sarcoidosis (1.3% DH and 1.8% CD), and vitiligo or alopecia areata (1.6% DH and 0% CD). We have shown that patients with DH are similar to those with CD in that many have associated endocrine or connective tissue disorders. Most of these diseases began before DH had been diagnosed suggesting that those on a gluten-free diet are not at special risk of contracting them. | |
| 9486405 | HLA class II phenotype controls diversification of the autoantibody response in primary Sj | 1998 Feb | The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP). In order to evaluate the role of the HLA class II phenotype in controlling diversification of this autoantibody response, 80 patients with pSS were typed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) at the HLA class II loci DRB1, DQA1 and DQB1. Serum samples were examined for anti-La and anti-Ro by counterimmunoelectrophoresis and by ELISA using purified recombinant La and 60-kD Ro proteins. Patient sera were classified according to the extent of diversification of the anti-La, anti-Ro response including the presence or absence of precipitating anti-La antibodies. Immunogenic characteristics of these stratified groups were then studied. All patients with pSS, with or without autoantibodies to Ro and La, were found to have at least one of the HLA-DRB1 types DR2, DR3 or DR5. The HLA DR3-DQA1*0501-DQB1*02 (DR3-DQ2) haplotype was primarily associated with a diversified La/Ro RNP response containing precipitating autoantibodies to La (P<0.001); whereas the haplotype HLA DR2-DQA1*0102-DQB1*0602 (DR2-DQ1) was associated with a less diversified La/Ro RNP response containing non-precipitating (restricted epitope) anti-La autoantibodies (P<0.001). Anti-La-positive patients lacking both HLA-DR2 and HLA-DR3 all expressed the HLA-DQA1*0501 allele, which was present at increasing frequency with greater diversification of the anti-La/Ro autoantibody response. The association of distinct HLA haplotypes with different degrees of autoantibody diversification in patients with pSS suggests a model of HLA-restricted presentation of La/Ro peptide determinants to autoreactive helper T cells. We propose that non-precipitating anti-La responses are driven by limited intermolecular help from DR2-DQ1-restricted T helper cells recognizing Ro determinants. On the other hand, we speculate that the more diversified, precipitating anti-La responses obtain more efficient cognate T help from DR3-DQ2-restricted T helper cells recognizing La determinants, where HLA-DQA1*0501 may be a critical determinant for antigen presentation. | |
| 9785988 | [A case of primary Sjögren's syndrome accompanied by transverse myelitis]. | 1998 Aug | Here we report a case of Sjögren's syndrome (SS) accompanied by transverse myelitis. A 46-year-old woman with 7-year history of primary SS was admitted to Tokyo Metropolitan Ohtsuka Hospital in September 1997 because of muscular weakness in lower extremities. She had had a low grade fever, numbness, and pain in bilateral lower extremities since July 1992. Neurological examination revealed transverse myelopathy at the level of Th 4, and peripheral neuropathy in lower extremities. Cerebrospinal fluid analysis showed slight elevation of protein and the cell count. A diagnosis of transverse myelitis and peripheral neuropathy presenting as neurologic manifestations of SS was made. Treatment was initiated with 30 mg of prednisolone, followed by improvement of fever and neurological findings. Although central nervous system complications of SS have been presented in Western countries, little information is available about Japanese patients. To our knowledge, this is the second case report which describes the occurrence of transverse myelitis in Japanese patients with SS. | |
| 9536818 | Weak association between subjective symptoms or and objective testing for dry eyes and dry | 1998 Jan | OBJECTIVES: To determine associations between symptoms of dry eyes and dry mouth and objective evidence of lacrimal and salivary gland dysfunction in a population based sample. To determine associations between these elements and the presence of autoantibodies. METHODS: A cross sectional population based survey. Subjects were interviewed and examined (Schirmer-1 test and unstimulated salivary flow) for the presence of dry eyes and mouth. Antibodies (anti-Ro [SS-A], anti-La [SS-B], rheumatoid factor, antinuclear antibody) were measured. RESULTS: 341 subjects were examined. Twenty four per cent had dry eye symptoms, 29% dry mouth symptoms, and 14% both. There was only a weak association between the presence of oral or ocular symptoms and their respective test results. Associations were strongest between dry mouth symptoms and positive test results, and in subjects under 55 years of age. There was no association between the presence of autoantibodies and either symptoms or signs of dry eyes or dry mouth. CONCLUSION: Only weak associations were found between self reported symptoms of dry eyes and dry mouth and objective measures said to define Sjögrens syndrome in the general population. The clinical significance of these symptoms in the community needs reappraisal. | |
| 11263785 | Elevated proapoptotic Bax and caspase 3 activation in the NOD.scid model of Sjögren's syn | 2001 Mar | OBJECTIVE: Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NODscid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-xL, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. METHODS: Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohistochemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. RESULTS: Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. CONCLUSION: These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS. | |
| 10949733 | Hypergammaglobulinemic purpura of Waldenström: report of 3 cases with a short review. | 2000 Jul | Benign hypergammaglobulinemic purpura of Waldenström (HGPW) is an uncommon cause of non-thrombocytopaenic purpura that may create diagnostic difficulties. The presence of constitutional symptoms associated with prominent immunological abnormalities may raise alarm, leading to extensive and often unnecessary investigations. This report describes 3 young women with HGPW. Clinical features were characterised by recurrent episodes of bilateral asymmetrical palpable purpuric lesions on the lower extremities that were precipitated by a prolonged increase in hydrostatic pressure (e.g. prolonged standing, tight stockings etc.) associated with constitutional features. In one patient the condition was secondary to Sjögren's syndrome with type IV renal tubular acidosis. Laboratory abnormalities included a persistently elevated erythrocyte sedimentation rate, marked polyclonal hypergammaglobulinemia, and high titers of rheumatoid factor and anti-nuclear antibody of the anti-SSA (anti-Ro)/anti-SSB(anti-La) subsets. This topic is reviewed briefly with the emphasis that in its 'primary' form this condition could be considered a 'benign' systemic immunoinflammatory disease that requires neither extensive investigations nor any aggressive form of therapy. Greater awareness of HGPW may increase the frequency of its diagnosis, especially in the patient group with non-thrombocytopenic purpura or the so-called cutaneous vasculitic syndromes with 'palpable purpura'. | |
| 10328193 | Anti-alpha-fodrin antibodies in Sjögren syndrome and lupus erythematosus. | 1999 May | OBJECTIVES: To investigate the prevalence of anti-alphafodrin antibody in patients with Sjogren syndrome (SS), lupus erythematosus (LE), or both and the association of this antibody with other clinical manifestations. DESIGN: A study of screening and diagnostic tests. Mean follow-up was 152 months (range, 4-572 months). SETTING: A university hospital associated with a research laboratory in Tokyo, Japan. PATIENTS: Nine patients with primary SS, 15 patients with SS secondary to LE, and 44 patients with LE alone. MAIN OUTCOME MEASURES: Frequencies of clinical and laboratory findings, including anti-alpha-fodrin antibody. RESULTS: Anti-alpha-fodrin antibody was more commonly detected in patients with primary (7/9; P<.001) and secondary (9/15; P<.001) SS than in those with LE alone (3/44). When patients with primary and secondary SS were combined and compared with those with LE alone, the sensitivity of anti-alpha-fodrin antibody was 67%, specificity was 93%, and both positive and negative predictive values were 84%. The presence of anti-alpha-fodrin antibody was associated with pernio, hyperglobulinemia, rheumatoid factor positivity, and the presence of anti-SS-B (La) antibody (P<.01) but not with annular erythema, photosensitivity, vasculitis, or renal disorder. CONCLUSIONS: Although anti-alpha-fodrin antibody was detected in patients with SS and in those with LE, it seemed to be more valuable for the diagnosis of SS than was anti-SS-A (Ro) because anti-alpha-fodrin was much less prevalent in patients with LE alone. It may be possible to consider this novel autoantibody as pathophysiologically associated with some extraglandular manifestations characteristically seen in patients with SS. | |
| 9726453 | MR sialography in patients with Sjögren syndrome. | 1998 Aug | PURPOSE: The purpose of this study was to evaluate the effectiveness of MR sialography of the parotid gland ducts in the diagnosis and staging of Sjögren syndrome. METHODS: MR imaging was performed on a 1.5-T unit with a neck phased-array coil. MR sialographic source images were obtained using a heavily T2-weighted fast spin-echo sequence with spectral fat suppression. All images were analyzed on the basis of maximum intensity projection reconstruction. Five healthy control subjects and 51 patients with definite Sjögren syndrome (43 with primary disease and eight with secondary disease) were examined with MR sialography. A labial gland biopsy was performed in all patients and histopathologic grading was done by means of focal scores. The findings of MR sialography were compared with the results of labial gland biopsy to determine the effectiveness of the technique in the diagnosis and staging of Sjögren syndrome. RESULTS: In all five control subjects, the main duct and the primary branching ducts of the parotid glands were clearly visible on MR sialographic images. In patients with Sjögren syndrome, a punctate, globular, cavitary, or destructive appearance was well seen within the parotid glands. Findings obtained at MR sialography correlated well with the results of labial gland biopsy. CONCLUSION: MR sialography has the potential to produce diagnostic findings in the parotid gland ducts of patients with Sjögren syndrome. Our results suggest that this method will augment and possibly replace X-ray sialography. | |
| 10393849 | Estrogen deficiency accelerates autoimmune exocrinopathy in murine Sjögren's syndrome thr | 1999 Jul | Estrogenic action has been suggested to be responsible for the strong female preponderance of autoimmune diseases, but the role of estrogens in the female has not been well characterized. We evaluated the effects of estrogen deficiency in a murine model for autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe destructive autoimmune lesions developed in the salivary and lacrimal glands in estrogen-deficient mice, and these lesions were recovered by estrogen administration. We detected an intense estrogen receptor in splenic CD8(+) T cells compared with that in CD4(+) T cells, and concanavalin-A-stimulated blastogenesis of splenic CD8(+) T cells with estrogens was much higher than that of CD4(+) T cells. We found a significant increase in serum autoantibody production against the organ-specific autoantigen alpha-fodrin. Moreover, an increased proportion of TUNEL+ apoptotic epithelial duct cells was observed in estrogen-deficient mice. It was demonstrated that Fas-mediated apoptosis in cultured salivary gland cells was clearly inhibited by estrogens in vitro. These results indicate that dysfunction of regulatory T cells by estrogen deficiency may play a crucial role on acceleration of organ-specific autoimmune lesions, and estrogenic action further influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS. | |
| 10025913 | Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. | 1999 Feb | The fine specificity of the Ro and La proteins has been studied by several techniques. In general, there is agreement in a qualitative sense that autoantibodies bind multiple epitopes. For some specific antibody binding, different studies agree quantitatively, for instance, the binding of the carboxyl terminus of 60-kd Ro as described by 2 studies using different techniques and the presence of an epitope within the leucine zipper of 52-kd Ro. In addition, there is general agreement about the location of a prominent epitope at the RRM motif region of the La molecule. On the other hand, the many specific epitope regions of the molecules differ among these studies. These discrepancies are likely the result of using different techniques, sera, and peptide constructs as well as a result of inherent advantages and disadvantages in the individual approaches. Several theories concerning the origin of not only the antibodies, but also the diseases themselves, have been generated from studies of the fine specificity of antibody binding. These include a theory of a primordial foreign antigen for anti-Ro autoimmunity, molecular mimicry with regard to La and CCHB, as well as the association of anti-Ro with HLA. These remain unproven, but are of continuing interest. An explanation for the association of anti-60-kd Ro and anti-52-kd Ro in the sera of patients has sprung from evaluating antibody binding. Data demonstrating multiple epitopes are part of a large body of evidence that strongly suggests an antigen-driven immune response. This means that the autoantigens are directly implicated in initiating and sustaining autoimmunity in their associated diseases. A number of studies have investigated the possibility of differences in the immune response to these antigens in SS and SLE sera. While several differences have been reported, none have been reproduced in a second cohort of patients. Furthermore, none of the reported differences may be sufficiently robust for clinical purposes, such as distinguishing between SS with systemic features and mild SLE, although some might be promising. For instance, in at least 3 groups of SLE patients, no binding of residues spanning amino acids 21-41 of 60-kd Ro has been found. Meanwhile, 1 of those studies found that 41% of sera from patients with primary SS bound the 60-kd Ro peptide 21-41. Perhaps future studies will elaborate a clinical role of such a difference among SS and SLE patients. Study of the epitopes of these autoantigens has, in part, led to a new animal model of anti-Ro and anti-La. Non-autoimmune-prone animals are immunized with proteins or peptides that make up the Ro/La RNP. Such animals develop an autoimmune response to the entire particle, not just the immunogen. This response has been hypothesized to arise from autoreactive B cells. In another, older animal model of disease, the MRL-lpr/lpr mouse, B cells have recently been shown to be required for the generation of abnormal, autoreactive T cells. Thus, there are now powerful data indicating that B cells that produce autoantibodies are directly involved in the pathogenesis of disease above and beyond the formation of immune complexes. Given that the autoreactive B cell is potentially critical to the underlying pathogenesis of disease, then studying these cells will be crucial to further understanding the origin of diseases associated with Ro and La autoimmunity. Hopefully, an increased understanding will eventually lead to improved treatment of patients. Progress in the area of treatment will almost surely be incremental, and studies of the fine specificity of autoantibody binding will be a part of the body of basic knowledge contributing to ultimate advancement. In the future, the animal models will need to be examined with regard to immunology and immunochemistry as well as genetics. The development of these autoantibodies has not been studied extensively because upon presentation to medical care, virtually all patients have a full- | |
| 11284994 | Chronic polyneuropathies in Vest-Agder, Norway. | 2001 Mar | Epidemiological data on chronic polyneuropathies, especially inflammatory types, is limited. The purpose of this study was to examine the spectrum of causes and estimated prevalence of various polyneuropathy types in Vest-Agder, and to examine the clinical features of the Vest-Agder population of chronic inflammatory demyelinating polyneuropathy (CIDP). In Vest-Agder county (population of 155 464), polyneuropathy patients are registered in a database and followed prospectively. We did a measure of the database on October 31 1999. A total of 192 patients were registered. The prevalence for chronic inflammatory demyelinating polyneuropathy (CIDP) was 7.7 per 100 000 population. The course was relapsing in five of fifteen patients, progressive in four patients and slowly progressive in six of fifteen patients. Two of the fifteen patients had pure sensory symptoms. The mean Rankin disability score was 3.4 at maximal deficit and 2.1 at last follow-up. The prevalence of paraproteinemic polyneuropathy was 5.1 per 100 000 population. None of the patients with paraproteinemic polyneuropathy were worse than slightly disabled (disability score < or = 2). The prevalences for other polyneuropathies were as follows: polyneuropathy and RA, 1.3; polyneuropathy and Sjögren's syndrome or sicca complex, 4.5 (polyneuropathy was the presenting symptom in five of seven patients); sarcoidosis 1.9; polyneuropathy and chronic Lyme, 0.6; paraneoplastic polyneuropathy, 1.9; diabetic polyneuropathy 23.2; vitamin deficiency, 5.1; alcoholic and toxic polyneuropathy, 19.9; hereditary polyneuropathy, 14.8. Cryptogenic polyneuropathies made up 26% of all polyneuropathies. The mean disability score was 2.0 (SD 1.1). In conclusion, prevalence of CIDP was significantly higher than previously reported, and the prognosis was good in the majority of patients. Patients with paraproteinemic polyneuropathy were not severely disabled. Polyneuropathy was the presenting symptom in the majority of patients with Sjögren's syndrome or sicca complex. | |
| 11280213 | [A case of Sjögren's syndrome presenting with hypokalemic myopathy due to renal tubular a | 2001 | A 37-year-old woman was admitted to our university hospital because of severe flaccid quadriplegia. Her laboratory data, lip biopsy and muscle biopsy findings were compatible with hypokalemic myopathy due to renal tubular acidosis(RTA) type I associated with primary Sjögren's syndrome. Kidney biopsy revealed chronic tubulointerstitial nephritis(TIN), consisting of focal mononuclear cell infiltration with tubulitis, interstitial fibrosis and tubular atrophy. Immunohistochemical analysis of the renal biopsy specimens showed that the infiltrating mononuclear cells were predominantly CD8+T cells, and CD68+ cells(macrophages), whereas CD4+ T cells were fewer in number. Following potassium administration and alkali therapy, hypokalemia and metabolic acidosis were ameliorated and limb palsy gradually subsided. Finally, RTA improved with prednisolon and short term cyclophosphamide treatment without supplemental potassium and alkali therapy. | |
| 11203926 | Effect of xerostomic medications on stimulated salivary flow rate in patients with Sjögre | 2000 Mar | OBJECTIVE: The purpose of this study was to examine the effect of xerostomic medications on the salivary output of patients with Sjögren's syndrome. METHOD AND MATERIALS: Of 62 patients evaluated in this study, 23 were not using medication, and 39 were using between 1 and 6 medications with xerostomic side effect. RESULTS: The mean +/- SEM stimulated parotid output was 0.33 +/- 0.07 mL/min per gland for patients who were not using medication and 0.33 +/- 0.04 mL/min per gland for patients using (1 to 6) medications. Analyses did not reveal a significant difference in salivary output between these groups. The salivary output of patients using various numbers of medications (1 or 2; 3 or 4; 5 or 6) was also compared. Analysis revealed no significant difference in salivary output related to the number of xerostomic medications used. CONCLUSION: The use of xerostomic medications may not necessarily affect stimulated parotid flow rate in patients with Sjögren's syndrome. These results suggested that gustatory stimulation may be adequate to overcome the inhibitory effect induced by xerostomic medications. | |
| 11061567 | Diagnostic value of the detection of t(14;18) chromosome translocation in malignant hemato | 2000 Oct | The majority of the t(14;18) chromosome translocations that occur in non-Hodgkin centroblastic-centrocytic follicular lymphoma can be detected by various methods. During the translocation process the bcl-2 gene located on chromosome 18 (18q21) is translocated to the JH region of the immunoglobulin gene of chromosome 14 (14q32). The most frequent type of bcl-2 translocations is the mbr type, whereas the immunoglobulin gene breaks mainly at the JH1-6 exons. About one of the 10(5) cells bearing the translocation can already be detected by using nested polymerase chain reaction (PCR). Eight patients suffering from follicular lymphoma were included in this study, which considered the usefulness of the PCR method. The results are in good agreement with those obtained by conventional diagnostic methods. Translocation can be detected, however, in patients with non-malignant diseases such as Sjögren's syndrome (about 5% of the patients) and in a patient with Whipple disease. In addition, translocation was detected in lymphocytes of peripheral blood of a healthy donor. Since lymphomas are detected in patients with Sjögren's syndrome with a relative high frequency, an early diagnosis of the translocation could improve the treatment of the disease. Nevertheless, a diagnosis of lymphoma is valid only in cases of bone marrow translocation-positivity. | |
| 9927792 | [Incidence and clinical features of splenic abscesses, with special reference to tuberculo | 1998 Dec | BACKGROUND: The aim of this revision is to know the incidence of splenic abscess (SA) in our hospital, its etiology, with special reference to tuberculosis, and clinical characteristics. PATIENTS AND METHODS: Abdominal CT-scan performed during the period 1987-1997, with the diagnosis of splenic abscess were reviewed. Etiologic diagnosis standed on blood or sputum cultures, PAAF and/or histologic study of lymph nodes. RESULTS: Seventeen cases of SA were obtained, 12 males and 5 females. Limits of age: 13 and 77 years. The causal microorganisms were: M. tuberculosis (7), Mycobacterium aviumintracellulare (1), S. aureus (2), S. anginosus (1), S. milleri (1), E. coli (1), C. albicans (1), T. biguelle (1) and polymicrobian flora (1). One case was of unknown etiology. Underlying illnesses were: AIDS (7), malignant neoplasms (3), diabetes (2), endocarditis (2), Sjögren syndrome (1) and complications of abdominal surgery (2). Clinical presentation in nontuberculous splenic abscess was fever and upper-left abdominal pain. Predominant symptoms in tuberculous splenic abscess were fever and weight loss. Blood cultures were positive in 80% of non tuberculous splenic abscess. Specific treatment for tuberculosis improved all patients with tuberculous splenic abscess, without needing surgery or corticosteroids. CONCLUSIONS: From the total of splenic abscess, 41.1% were tuberculous, six with AIDS and one with Sjögren syndrome. Diabetes and malignant neoplasms were the commonest underlying illnesses in the non-tuberculous. In these, clinical presentation consisted in fever and upper-left abdominal pain. In patients with tuberculous splenic abscess, the main complaint was weight loss. A prompt treatment is generally succesful. | |
| 9894474 | Lymphoid proliferations of the salivary glands. | 1999 Jan | Lymphoid proliferations of the salivary glands can be either reactive or neoplastic. Reactive lesions include cystic lymphoid hyperplasia--a multicystic ductal proliferation with reactive germinal centers, seen most often in intravenous drug users infected with HIV--and the lymphoepithelial sialadenitis of Sjögren's syndrome (so-called benign lymphoepithelial lesion [BLEL] or myoepithelial sialadenitis [MESA]). This lymphoid proliferation involves infiltration of ductal epithelium by lymphocytes of marginal zone or monocytoid B-cell type, forming lymphoepithelial lesions (epimyoepithelial islands). Patients with lymphoepithelial sialadenitis have a 44-fold increased risk of developing salivary gland or extrasalivary lymphoma, of which 80% are marginal zone/MALT type. Broad strands of marginal zone or monocytoid B cells around lymphoepithelial lesions and monotypic immunoglobulin detection by immunohistochemistry are considered diagnostic of MALT lymphoma. B-cell clones are detected in over 50% of cases of MESA by molecular genetic methods, but this does not correlate with overlymphoma. "Nodal" type B-cell lymphomas of the salivary glands are either follicular lymphoma (35%), which may arise in intrasalivary gland lymph nodes and behave similarly to follicular lymphoma in other sites, or diffuse large B-cell lymphoma (30%), which may arise de novo or secondary to either MALT or follicular lymphomas. | |
| 9146866 | The establishment of a xerostomia clinic: a prospective study. | 1997 Apr | The study investigated the aetiological factors and management of patients who have xerostomia. The subjects were 100 consecutive patients referred to the Oral Medicine Unit for investigation of oral dryness. A detailed case history was recorded and patients underwent a systematic examination together with sialometry, haematological, biochemical and immunological investigations. Suspected cases of Sjögren's syndrome (SS) were referred for assessment by a rheumatologist and ophthalmologist. Objective evidence of salivary gland hypofunction was found in 39 patients. A definite diagnosis of primary and secondary SS was made in 24 and 15 patients respectively, a further five cases had possible primary SS. Other causes of xerostomia were: undiagnosed diabetes (3); drug-induced (11); therapeutic radiation (3); alcohol-related (3); psychogenic (15) and idiopathic (21). Patients complaining of a dry mouth should be questioned about non-oral symptoms. In total, 40% of patients attending the dry mouth clinic had a diagnosis of SS. | |
| 9191982 | Androgen stimulation of lacrimal gland function in mouse models of Sjögren's syndrome. | 1997 Feb | Sjögren's syndrome, an autoimmune disease that occurs primarily in women, causes extensive inflammation and significant dysfunction in the lacrimal gland, and is one of the leading causes of dry eye syndromes throughout the world. Recently, our research has shown that androgen treatment causes a significant suppression of the immunopathological lesions in lacrimal tissues of female mouse models (MRL/Mp-lpr/lpr [MRL/lpr] and NZB/NZW F1 [F1]) of Sjögren's syndrome. To extend these findings, the objective of the present study was to determine whether this androgen-induced anti-inflammatory action may be paralleled by an increase in the functional activity of lacrimal glands in these autoimmune mice. Towards this end, we measured the tear levels of immunoglobulin A (IgA), which originates from lacrimal tissue and whose concentration is known to be diminished in mucosal sites in Sjögren's syndrome. For comparative purposes, we also evaluated whether the administration of other steroid hormones or immunosuppressive agents might duplicate possible androgen effects on the secretory function of lacrimal tissue. Female MRL/lpr and F1, as well as non-autoimmune BALB/c, mice were treated with vehicle, steroids or immunosuppressive compounds for 17 to 54 days after the onset of disease. Lacrimal glands, tears and sera were collected immediately before (pretreatment), or after, therapy and processed for the analysis of either tear IgA (enzyme-linked immunosorbent assay; ELISA) and protein content or the magnitude of lymphocyte infiltration (computer-assisted image analysis). Our findings demonstrated that testosterone treatment stimulated a significant increase in the concentration and total amount of tear IgA, as well as tear protein, compared to levels in pretreatment or placebo controls. This hormone action was reproduced by exposure to a diverse array of "anabolic" and "androgenic" androgen analogues, but not by treatment with estradiol, danazol, cyclosporine A, dexamethasone or cyclophosphamide. In contrast, only dexamethasone increased serum IgA concentrations. Of particular interest is the fact that the androgen control of IgA output by the lacrimal gland appeared to be independent of this steroid's suppression of lymphocyte infiltration in lacrimal tissue. Overall, these results show that androgen therapy enhances the functional activity of the lacrimal gland in mouse models of Sjögren's syndrome. |