Renal lesions in IgG4-related systemic disease.
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OBJECTIVE: Recently, a new concept of IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high serum IgG4 level and tissue infiltration by IgG4-positive plasma cells, has been proposed. Our aim was to investigate the renal involvement in this condition. PATIENTS AND METHODS: We investigated the results of laboratory and imaging studies of the kidneys in 7 patients with IgG4-related systemic disease, and examined the renal histology in four of them. All patients showed elevated serum IgG4 levels, and 4 had autoimmune pancreatitis. The other three patients showed involvement of various extrapancreatic organs (lymphadenopathy, sialadenitis or renal insufficiency), and abundant IgG4-positive plasma cell infiltration was confirmed in their affected tissues. RESULTS: Six of the 7 patients showed some renal abnormalities. In one patient, hydronephrosis was observed accompanied by retroperitoneal fibrosis. Another patient showed multiple low-density areas in both kidneys by computed tomography, and gallium citrate scintigraphy showed gallium-67 accumulation in both kidneys, although renal function was normal. Four patients had tubulointerstitial nephritis. In two of them, the tubulointerstitial nephritis was diffuse. In one patient, marked diffuse but patchily distributed lymphoplasmacytic infiltration of the renal interstitium was observed. In another patient, computed tomography showed a tumor-like low-density mass; open biopsy of the mass showed aggregates of lymphocytes and plasma cells in the renal interstitium. CONCLUSION: Renal parenchymal lesions in IgG4-related systemic disease are due to dense lymphoplasmacytic infiltration of the renal interstitium, and the lesions vary from diffuse tubulointerstitial nephritis to tumor-like masses according to the distribution patterns of the infiltrating cells. (+info)
Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjogren's syndrome.
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Demonstration of ectopic germinal center-like structures (GC-LSs) in chronically inflamed tissues in patients with autoimmune disorders is a relatively common finding. However, to what extent ectopic lymphoid structures behave as true GC and are able to support class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes is still debated. In addition, no information is available on whether CSR and SHM can take place in the absence of GCs at extrafollicular sites in an ectopic lymphoid tissue. In this study, we show that in salivary glands (SGs) of Sjogren's syndrome (SS) activation-induced cytidine deaminase (AID), the enzyme responsible for CSR and SHM is invariably expressed within follicular dendritic cell (FDC) networks but is not detectable in SGs in the absence of ectopic GC-LSs, suggesting that FDC networks play an essential role in sustaining the Ag-driven B cell proliferation within SS-SGs. We also show that the recently described population of interfollicular large B cells selectively expresses AID outside ectopic GC in the T cell-rich areas of periductal aggregates. Finally, we report that AID retains its exclusive association with numerous, residual GCs in parotid SS-MALT lymphomas, whereas neoplastic marginal zone-like B cells are consistently AID negative. These results strongly support the notion that ectopic lymphoid structures in SS-SGs express the molecular machinery to support local autoantibody production and B cell expansion and may play a crucial role toward lymphomagenesis. (+info)
The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice.
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The nonobese diabetic (NOD) Nss1 and Idd5 loci have been associated with sialadenitis development in mice. In this study the NOD Nss1 and Idd5 loci were backcrossed onto the healthy control strain B10.Q by using the speed congenic breeding strategy, resulting in three congenic strains: B10.Q.Nss1, B10.Q.Nss1/Idd5 heterozygous and B10.Q.Nss1/Idd5 homozygous. We investigated the effects of the Nss1 and Idd5 loci on sialadenitis and gene expression in NOD congenic mice. One submandibular salivary gland from each mouse was used for histological analysis of sialadenitis, whereas the contralateral salivary gland was used for gene expression profiling with the Applied Biosystems Mouse Genome Survey chip v.1.0. The results were validated using quantitative reverse transcriptase PCR. The NOD Nss1 and Idd5 loci had clear influence on the onset and progression of sialadenitis in congenic mice. Double congenic mice exhibited the most severe phenotype. We successfully identified several genes that are located in the NOD congenic regions to be differentially expressed between the congenic strains and the control strain. Several of these were found to be co-regulated, such as Stat1, complement component C1q genes and Tlr12. Also, a vast contingency of interferon-regulated genes (such as Ltb, Irf7 and Irf8) and cytokine and chemokine genes (such as Ccr7 and Ccl19) were differentially expressed between the congenic strains and the control strain. Over-representation of inflammatory signalling pathways was observed among the differentially expressed genes. We have found that the introgression of the NOD loci Nss1 and Idd5 on a healthy background caused sialadenitis in NOD congenic mouse strains, and we propose that genes within these loci are important factors in the pathogenesis. Furthermore, gene expression profiling has revealed several differentially expressed genes within and outside the NOD loci that are similar to genes found to be differentially expressed in patients with Sjogren's syndrome, and as such are interesting candidates for investigation to enhance our understanding of disease mechanisms and to develop future therapies. (+info)
Lymphoid lesions of salivary glands: malignant and benign.
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Lesions of salivary glands with a prominent lymphoid component are a heterogeneous group of diseases that include benign reactive lesions and malignant neoplasms. Occasionally, these pathologic entities present difficulties in the clinical and pathological diagnosis and prognosis. Lymphoepithelial sialadenitis, HIV-associated salivary gland disease, chronic sclerosing sialadenitis, Warthin tumor, and extranodal marginal zone B-cell lymphoma are examples of this pathology that are sometimes problematic to differentiate from one another. In this paper the author reviewed the main clinical, pathological and prognostic features of these lesions. (+info)
Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation.
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Kuttner's tumour (chronic sclerosing sialadenitis) of the submandibular gland: a clinical perspective.
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OBJECTIVE: To study clinical perspectives pertaining to chronic sclerosing sialadenitis, which is also known as Kuttner's tumour. DESIGN: Retrospective medical chart review. SETTING: Regional hospital, Hong Kong. PATIENTS: From February 2005 to February 2007, nine cases with Kuttner's tumour were identified from our hospital electronic database. INTERVENTIONS: They underwent submandibular sialadenectomy under either local (n=6) or general (n=3) anaesthesia. MAIN OUTCOME MEASURES: The results of preoperative ultrasonography, fine-needle aspiration cytology, and intra-operative frozen section examination were correlated with the final diagnosis. Operative morbidity was also evaluated. RESULTS: The mean age of the patients at diagnosis was 61 years; three were females. Three had bilateral submandibular swellings. Following preoperative ultrasonography in six of the patients, tumours were suspected in two, an enlarged lymph node in one, and diffuse enlargement was visualised in the other three. Six patients had preoperative fine-needle aspiration cytology; five yielded scanty acini with normal-looking ductal cells, variable degrees of infiltration by chronic inflammatory cells without granuloma admixing fibrosis. In the sixth patient, only bland-looking epithelial cells, indicative of ductal differentiation suspicious of neoplasm were noted. Intra-operative frozen section examination was conducted in three patients: chronic inflammation without evidence of carcinoma was visualised in each. Operations performed under local anaesthesia were well tolerated; only one patient endured a transient, marginal facial nerve palsy. CONCLUSIONS: Kuttner's tumour is by no means rare. When supported by ultrasonography and fine-needle aspiration cytology, an accurate diagnosis can be made preoperatively and surgery can be reserved for symptomatic cases. Submandibular sialadenectomy is a safe and effective means of treating Kuttner's tumour, and can be accomplished under local anaesthesia. (+info)
Biomarker profiles in serum and saliva of experimental Sjogren's syndrome: associations with specific autoimmune manifestations.
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