Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
Autoimmune Diseases/*immunology ; Cholangitis, Sclerosing/*immunology ; Humans ; Immunoglobulin G/*immunology ; Lacrimal Apparatus/immunology ; Lymphatic Diseases/*immunology ; Pancreatitis, Chronic/*immunology ; Salivary Glands/immunology ; Sclerosis/immunology

In the present study, normal guinea pigs were used to investigate the possible pathogenic role of cell-mediated immunity in Sjogren's syndrome. The effects of anti-salivary gland antibodies on circulating lymphocytes, various organs including salivary glands, thymus and the reticuloendothelial system, and on delayed hypersensitivity were studied. Our study demonstrated that anti-salivary gland antibodies directly affected circulating lymphocytes. There was a 60-80% decrease in the lymphocyte count from the original level with a maximum effect at 5 hours after the introduction of the antibodies. When antibodies were injected repeatedly, the recovery to the pre-injection level of lymphocytes was delayed. We also found that antisalivary g1and antibodies were not organ-specific and were cross-reactive with various organs that are often involved in Sjogren's syndrome. Direct immunofluorescent study showed antibody deposits in the thymus-dependent areas of lymph nodes. These results suggest that antisalivary gland antibodies are lymphocytotoxic and have an anti-T cell property. The anti-salivary gland antibodies prepared in this experiment did not produce any pathological lesions such as those found in Sjogren's syndrome. The amount of antiserum or the period of administration might not have been long enough to produce pathological changes. Another possibility is that the anti-salivary gland antibodies might be species-specific. On the basis of these results, it appears that impaired cell-mediated immunity is not the primary pathogenic factor responsible for Sjogern's syndrome but rather that deranged immunity is secondary to the development of anti-salivary gland antibodies which occur in Sjogern's syndrome.
Animal ; Antibodies* ; Guinea Pigs ; Hypersensitivity, Delayed ; Leukocyte Count ; Lymphocytes/immunology* ; Rabbits ; Reticuloendothelial System/immunology ; Salivary Glands/immunology* ; Sjogren's Syndrome/immunology ; T-Lymphocytes/immunology

BACKGROUNDTo study the composition and significance of the inclusion bodies of human cytomegalovirus (HCMV).

METHODSMicrodissection of inclusion bodies, PCR and Southern blot were adopted to detect DNA, and immunohistochemistry method and catalyzed signal amplification (CSA) were used to detect the different antigens of HCMV.

RESULTSThe inclusion bodies of HCMV were separated from the tissue section of human salivary gland. The fragments amplified by PCR from these dissected inclusion bodies were confirmed to be the DNA of HCMV. With the immunohistochemical method CSA, the immediately early and early antigens of HCMV were detected with monoclonal antibodies DDG9/CCH2, while matrix protein AAC10 was negative in the inclusion bodies.

CONCLUSIONThe ingredient of inclusion bodies of HCMV included the DNA and the antigens expressed in specific stage of the virus.

Antigens, Viral ; analysis ; immunology ; Cytomegalovirus ; genetics ; immunology ; Cytomegalovirus Infections ; diagnosis ; immunology ; virology ; DNA, Viral ; analysis ; genetics ; Humans ; Immunohistochemistry ; Inclusion Bodies ; chemistry ; immunology ; virology ; Microdissection ; Salivary Glands ; chemistry ; immunology ; virology

OBJECTIVETo study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS).

METHODSA total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls.

RESULTSThere were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P<0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P<0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P<0.05).

CONCLUSIONSIgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

Adult ; Aged ; Chronic Disease ; Female ; Humans ; Immunoglobulin G ; blood ; Immunohistochemistry ; Lacrimal Apparatus ; pathology ; Male ; Middle Aged ; Nasal Mucosa ; pathology ; Paranasal Sinuses ; pathology ; Rhinitis ; diagnosis ; immunology ; Salivary Glands ; pathology ; Sialadenitis ; diagnosis ; immunology ; Sinusitis ; diagnosis ; immunology

OBJECTIVEThe aim of this study was to investigate the mechanism(MDR) of multidrug resistance(MDR) of mucoepidermoid carcinoma in salivary gland.

METHODS40 cases of mucoepidermoid carcinoma in salivary gland were examined the MDR gene product P-glycoprotein using a monoclonal antibody JSB-1. And 10 of them were also investigated by detecting the expression of GST-pi. All the cases had not been accepted any therapy before the samples were collected.

RESULTS1. Positive expression of JSB-1 was observed in 27 of the 40 specimens. The positive expression was related not only with clinical stage, but also with differentiation degree. 2. The GST-pi positive expression was found in 9 of 10 cases. There was no significant different between the positive expression of JSB-1 and GST-pi.

CONCLUSIONJSB-1 and GST-pi play an important role in MDR of mucoepidermoid carcinoma.

ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Adolescent ; Adult ; Aged ; Antibodies, Monoclonal ; analysis ; Carcinoma, Mucoepidermoid ; immunology ; Child ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Female ; Genes, MDR ; Glutathione S-Transferase pi ; Glutathione Transferase ; analysis ; Humans ; Isoenzymes ; analysis ; Male ; Middle Aged ; Salivary Gland Neoplasms ; immunology ; Salivary Glands ; immunology

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

BACKGROUNDSjögren syndrome (SS) is an autoimmune disorder characterized by chronic lymphocytic infiltration and decreased secretion in salivary glands. Apoptosis is one of the possible mechanisms involved in acinar epithelial destruction in SS. The role of apoptosis in the initiation and effect phase of sialoadenitis is still controversial. The aim of this study was to observe the roles of apoptosis-associated proteins and serum IgG levels in sialoadenitis progression in nonobese diabetic (NOD) mice.

METHODS2-, 5-, 10-, 15-, 20-week female NOD and matched BALB/c control mice were selected. Saliva and tear flow rate were measured. Serum IgG level was tested by enzyme-linked immunosorbent assay (ELISA). Number of lymphocyte foci (NLF) in submandibular glands (SMGs) was counted under routine hematoxylin/eosin-stained sections. Expression of Fas, Bcl-2 and procaspase3 proteins as well as apoptotic cells in the SMGs were detected by immunohistochemical staining and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay respectively.

RESULTSDecreased stimulated total flow rate (STFR) and lymphocyte foci in SMGs were first observed in the 10-week NOD group. STFR was negatively correlated with NLF (P < 0.05). Serum IgG in NOD mice was significantly higher than that of the control group (P < 0.05) and showed a positive correlation with NLF (P < 0.05). Fas expression in SMGs acinar cells in NOD mice increased with age and was significantly higher compared with that in the control group. Bcl-2 expression and procaspase3 expression in SMG acinar cells in each NOD group were lower compared with those of the age-matched control mice.

CONCLUSIONAbnormal expression of Fas and Bcl-2 in the SMGs and higher level of serum IgG may contribute to the initiation of sialoadenitis and cause the glandular destruction in NOD mice.

Animals ; Apoptosis ; Caspase 3 ; analysis ; Disease Progression ; Female ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Salivary Glands ; pathology ; Sialadenitis ; etiology ; immunology ; pathology ; Submandibular Gland ; chemistry ; fas Receptor ; analysis

The present study was designed to identify immunomodulatory components from the leech salivary gland of Haemadipsa sylvestris. The Sephadex G-50, Resource(TM) S column chromatography and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify the salivary gland extracts (SGE). Structural analysis of isolated compounds was based on Edman degradation and matrix assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). The cDNA encoding the precursor of the compound was cloned from the cDNA library of the salivary gland of H. sylvestris. The levels of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were assayed using an enzyme-linked immunosorbent assay (ELISA). The effects on cell proliferation and cell viability were observed using MTT assay. A novel neuropeptide Y (Neuropeptide Y-HS) from the leech salivary gland of H. sylvestris was purified and characterized. It was composed of 36 amino acid residues and the amino acid sequence was determined to be FLEPPERPAVFTSVEQMKSYIKALNDYYLLLGRPRF-NH2, containing an amidated C-terminus. It showed significant inhibitory effects on the production of inflammatory cytokines including TNF-α, IFN-γ, IL-6, and MCP-1. Neuropeptide Y was identified from leeches for the first time. The presence of neuropeptide Y-HS in leech salivary gland may help get blood meal from hosts and inhibit inflammation.
Amino Acid Sequence ; Animals ; Immunologic Factors ; administration & dosage ; chemistry ; genetics ; Inflammation ; drug therapy ; immunology ; Interferon-gamma ; immunology ; Interleukin-6 ; immunology ; Leeches ; chemistry ; Mass Spectrometry ; Mice ; Molecular Sequence Data ; Neuropeptide Y ; administration & dosage ; chemistry ; genetics ; Peptide Mapping ; Salivary Glands ; chemistry ; Tumor Necrosis Factor-alpha ; immunology