Annular erythema (AE) associated with anti-Ro (SSA) and/or La (SSB) autoantibody in patients with Sjogren syndrome (SS) or with SS/systemic lupus erythematosus overlap syndrome (SS/SLE), has recently been described in Orientals, and it may be a counterpart of annular skin lesion of the subacute cutaneous LE seen mostly in Caucasians. The author examined five Korean AE patients in respect to dinical diversity. In this small-sample study, subtle differences appeared between individual cases regarding the serologic features and the diagnoses of the disease. Among the five cases, four had circulating anti-Ro and anti-La antibodies, and one had only anti-La. Regarding the diagnosis, one was SS/SLE, two were primary SS, and the remaining two were only "AE associated with anti-Ro/La antibody". There seem to be a wide clinical spectrum in the disease expression of AE associated with anti-Ro/La autoantibody than previously thought.
Adolescence ; Adult ; Antibodies, Antinuclear/immunology* ; Case Report ; Erythema/immunology* ; Erythema/etiology ; Female ; Human ; Lupus Erythematosus, Systemic/immunology* ; Lupus Erythematosus, Systemic/complications ; Male ; Sjogren's Syndrome/immunology* ; Sjogren's Syndrome/complications

Adolescent ; Antibodies, Antinuclear ; blood ; Child ; Female ; Humans ; Sjogren's Syndrome ; diagnosis ; immunology ; therapy

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

OBJECTIVETo investigate the dynamic changes of lymphocyte subsets before and after autologous hemopoietic stem cell transplantation (HSCT) in severe/refractory autoimmune disease (AID) and study the post-transplantation immunological reconstitution in AID.

METHODSThirteen patients with severe/refractory AID who registered for HSCT from April 2003 to April 2005 in Peking Union Medical College Hospital, including 8 patients with systemic lupus erythematosus, 4 patients with rheumatoid arthritis, and 1 patient with primary Sjögren's syndrome (pSS) were enrolled in this study. Blood samples were collected before/after mobilization, before conditioning, and 2 weeks, 1 month, 3 months, 6 months, 12 months, and 18 months post-transplantation. Lymphocyte subsets were tested by flow cytometry as follows: T cell (CD3 +), B cell (CD19 +), natural killer (CD3-CD16 + CD56 +), Th (CD3 + CD4 +), Tc (CD3 + CD8 +), naïve T (CD4 + CD45RA), memory T (CD4 + CD45RO), and CD4/CD8 ratio.

RESULTSLymphocyte subsets for SLE patients were severely abnormal compared to normal or RA patients (both P < 0.01). B cell reconstituted to normal level within 18 months, meanwhile NK and T cell remained low. The repopulations of Th and naive T cell were delayed, which caused the up-side-down of CD4/CD8 ratio and low level of naYve T cell percentage for a relatively long time.

CONCLUSIONSLymphocyte subsets abnormality in SLE patients are more severe than in RA patients. Although most autoimmune T/B cell in the grafts and patients can be effectively removed after transplantation, nonmyeloablative conditioning may be a risk for the relapse of AID. The long-term inhibition of CD4 + T cell may be related with the relief of AID after transplantation.

Arthritis, Rheumatoid ; blood ; immunology ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Lupus Erythematosus, Systemic ; blood ; immunology ; therapy ; Lymphocyte Subsets ; immunology ; pathology ; Sjogren's Syndrome ; immunology ; therapy

Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT)-type is a very rare disease with distinct clinicopathologic features. I herein report a rare case of primary thymic MZBL of MALT-type arising in the thymus in a patient with Sjogren's syndrome and rheumatoid arthritis. A mediastinal mass was detected by computerized tomography in a 43-yr-old Korean woman with a history of Sjogren's syndrome and rheumatoid arthritis and the thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating the Hassall's corpuscles. Immunohistochemically, the tumor cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10, CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma cells in the tumor. Sjogren's syndrome and rheumatoid arthritis are known to be associated with MALT lymphoma and were considered to play an important role in the development of malignant lymphoma in this patient.
Adult ; Arthritis, Rheumatoid/*complications/immunology ; B-Lymphocytes/metabolism ; Female ; Human ; Lymphoma, Mucosa-Associated Lymphoid Tissue/diagnosis/*etiology/immunology ; Sjogren's Syndrome/*complications/immunology ; Thymus Neoplasms/immunology/*pathology ; Tumor Markers, Biological

OBJECTIVETo observe the effect of Yangyin Yiqi Huoxue Recipe (YYHR) on expression of interferon-gamma (IFN-gamma), IL-2, IL-4, IL-10, and immune balance of Th1/Th2 in serum and submaxillary glands of non-obese diabetic (NOD) mice with Sjogren's syndrome (SS), and to explore its mechanisms.

METHODSTotally 32 NOD mice were randomly into 4 groups, i.e., the model group, the Chinese medicine group [CM, administered with YYHR at the dose of 0.4 mL by gavage (100 g/kg)], the Western medicine group [WM group, administered with hydroxychloroquine 0.4 mL by gavage (60 mg/kg)], and the combined group [administered with YYHR (50 g/kg) and hydroxychloroquine (60 mg/kg) 0.4 mL by gavage], 8 mice in each group. Eight Balb/C mice were recruited as the normal control group. Mice were sacrificed to withdraw blood after 8 weeks. The submaxillary gland was excised. Serum levels of IFN-gamma, IL-2, IL-4, and IL-10 were detected by ELISA. Protein expression of IFN-gamma, IL-2, IL-4, and IL-10 in submaxillary glands was detected by SP method.

RESULTSCompared with the normal group, levels of IFN-gamma, IL-2, IL-4, and IL-10 in serum and submaxillary glands all increased in the model group (P < 0.05). Levels of IFN-gamma and IL-10 in serum in the CM group and the combined group were lower than those of the WM group (P < 0.05). Serum levels of IFN-gamma and IL-2 in submaxillary glands in combined group were lower than those of the WM group (P < 0.05). The ratio of IFN-gamma/IL-4 in serum and submaxillary glands in the model group were higher than that of the rest groups (P < 0.05). Besides, it was the nearest to that of the normal group.

CONCLUSIONSYYHR could decrease the levels of Th1 and Th2 related cytokines and the ratio of IFN-gamma/IL-4 in serum and submaxillary glands of NOD mice with SS. It could achieve therapeutic effects through adjusting immune balance of Th1/Th2 in SS mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interferon-gamma ; blood ; Interleukins ; blood ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Serum ; immunology ; Sjogren's Syndrome ; blood ; drug therapy ; immunology ; Submandibular Gland ; immunology ; Th1-Th2 Balance

OBJECTIVE: To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice. METHODS: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction. RESULTS: Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05). CONCLUSIONS ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.
Animals ; Cytokines ; blood ; Drugs, Chinese Herbal ; pharmacology ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Salivation ; drug effects ; Sjogren's Syndrome ; drug therapy ; immunology ; Submandibular Gland ; drug effects ; pathology ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Vasoactive Intestinal Peptide ; genetics

Anti-Ro autoantibody is associated with Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and neonatal lupus syndrome (i.e., congenital complete heart block in newborns). Generally, the adult atrioventricular (AV) node is believed to be relatively resistant to the scarring effects of anti-Ro/anti-La autoantibodies. However, there have been some reports of adult complete AV block in SS and SLE patients. Here, we report a case of complete heart block in primary SS with anti-Ro autoantibodies, with no other risk factor for the development of heart block, and review their etiological association.
Antibodies, Antinuclear/*blood ; Atrioventricular Block/diagnosis/*immunology/therapy ; Cardiac Pacing, Artificial ; Electrocardiography ; Electrocardiography, Ambulatory ; Exercise Test ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; Sjogren's Syndrome/complications/*immunology ; Treatment Outcome

BACKGROUNDAntibodies against type 3 muscarinic acetylcholine receptor (M3R) are involved in the pathogenesis of Sjögren's syndrome (SS), but the clinical value of them in SS patients has been controversial. The aims of this study were to: (1) establish an improved enzyme-linked immunosorbent assay (ELISA) to detect IgA antibodies against M3R; (2) evaluate the value of IgA antibodies against the second extracellular loop of M3R205-220 (c2M3RP) in diagnosis of SS.

METHODSTo increase the ELISA sensitivity, c2M3RP was coupled to bovine serum albumin (BSA) by the glutaraldehyde method and a 96-well microplate was treated by ultraviolet rays before coated. Concentrations of anti-c2M3RP, anti-SSA, and anti-SSB were measured in the sera of 240 individuals: 91 patients with primary SS and 149 controls (16 secondary SS, 27 systemic lupus erythematosus, 40 rheumatoid arthritis and 66 healthy controls). Diagnostic properties of anti-c2M3RP were determined by receiver-operating characteristic curve analysis.

RESULTSThe prevalence of serum IgA anti-c2M3RP antibodies in patients with pSS (46%, 42/91) was significantly higher than that in patients with systemic lupus erythematosus (19%, 5/27), in rheumatoid arthritis (15%, 6/40) and in healthy controls (5%, 3/66). However, there was no significant difference between the two SS groups (P = 0.727). The diagnostic performance of IgA anti-M3RP antibodies was similar to anti-SSA assay, but had 22% higher sensitivity than anti-SSB. By analyzing of IgA anti-c2M3RP antibodies, combination of anti-SSA and anti-SSB resulted in increased sensitivity, whereas their specificity was not significantly changed.

CONCLUSIONSThe improved anti-c2M3RP ELISA is a novel, sensitive, and specific serological test for the diagnosis of SS. The combined application of anti-c2M3RP, anti-SSA and anti-SSB tests can improve the laboratory diagnosis of SS. The IgA anti-c2M3RP antibodies may serve as a novel diagnostic marker for SS.

Adult ; Aged ; Aged, 80 and over ; Animals ; Autoantibodies ; immunology ; Biomarkers ; blood ; Cattle ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Humans ; Immunoglobulin A ; blood ; Male ; Middle Aged ; Receptors, Muscarinic ; immunology ; Sjogren's Syndrome ; blood ; Young Adult

OBJECTIVETo investigate the immuno-regulatory and therapeutic effects of Chinese herbal medicine for Yiqi Yangyin Quyu (YYQ, supplementing qi, nourishing yin, removing blood stasis) on Sjögren's syndrome (SS).

METHODSSixty-two patients were randomly divided into the treated group (37 cases) treated with Chinese medicine and prednisone, and the control group (25 cases) treated with prednisone alone, and another 20 healthy persons were taken as the normal control group. Curative effects was observed, and immunoglobulin (Ig) and T lymphocyte subsets were detected before and after 3 months' treatment.

RESULTSImmunoglobulin (IgG, IgM and IgA) before treatment in SS patients were higher, while the proportion of natural killer (NK) cell and CD4 were lower as compared with those in the normal control group. After treatment, IgG, IgM and IgA lowered to normal levels (P < 0.05), the proportion of NK cell and CD4 rose in both groups (P < 0.05), but CD3 in the control group was still lower than that in the treated group (P < 0.05). The total curative effective rate in the treated group was 91.9%, better than that in the control group (76.0%, chi-squared = 3.92, P < 0.05).

CONCLUSIONChinese herbal medicine for YYQ could improve clinical curative effective rate and regulate immune function in SS patients.

Adult ; Aged ; Anti-Inflammatory Agents ; therapeutic use ; CD4 Antigens ; immunology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulins ; immunology ; Killer Cells, Natural ; drug effects ; immunology ; Male ; Middle Aged ; Phytotherapy ; Prednisone ; therapeutic use ; Sjogren's Syndrome ; drug therapy ; immunology ; Yin Deficiency ; drug therapy ; immunology