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ID PMID Title PublicationDate abstract
8488407 Multiple myeloma and AL amyloidosis mimicking Sjögren's syndrome. 1993 May A 49-year-old white man had xerostomia, orthostatic hypotension, salivary gland enlargement, and a monoclonal gammopathy. Salivary gland biopsy revealed AL amyloidosis without histopathologic evidence of Sjögren's syndrome; serologic evidence of Sjögren's syndrome was also absent. Bone marrow biopsy revealed more than 30% plasma cells, and a diagnosis of multiple myeloma was made. The association of myeloma amyloidosis with salivary gland infiltration and xerostomia is rare. Unusual causes of xerostomia, such as myeloma amyloidosis, should be considered when histopathologic and serologic evidence of Sjögren's syndrome are absent.
1512299 Conjunctival epithelial cells from patients with Sjögren's syndrome inappropriately expre 1992 Jul The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjögren's syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls.
8544642 Primary biliary cirrhosis: lung involvement. 1995 Aug Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
8195302 A peripheral protein associated with the cis-Golgi network redistributes in the intermedia 1994 Jun Human autoantibodies offer unique tools for the study of cellular constituents since they usually recognize highly conserved components, the most difficult to detect due to their low immunogenicity. The serum from a patient with Sjögren's syndrome (RM serum) showing a very high reactivity to the Golgi complex has been shown to immunoprecipitate and to immunodetect by Western blotting experiments a protein mol wt 210,000 (p210) that was shown to be peripheral and cytoplasmically disposed. A close examination of the p210 labeling revealed some differences with Golgi markers: RM serum staining was slightly more extensive than several Golgi markers and showed a discontinuous or granular appearance. Nocodazole induced a specific and early segregation of many p210-associated vesicles or tubules from Golgi apparatus. Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins. In contrast, it exhibited a vesicular pattern reminiscent to that displayed by proteins residing in the intermediate compartment. Double staining immunofluorescence using the RM serum and the marker of the intermediate compartment, p58, revealed segregation of both proteins in control conditions but colocalization in BFA-treated cells. We have further demonstrated by combining different drug treatments that p210-containing elements in brefeldin A-treated cells belong indeed to the intermediate compartment. Experiments on brefeldin A recovery suggested that these p210 elements might play a role in reformation and repositioning of the Golgi apparatus. Ultrastructural localization performed by immunoperoxidase staining allowed us to establish that p210 interacted with the external side of an abundant tubulo-vesicular system on the cis side of the Golgi complex which extended to connecting structures and vesicles between saccules or stacks of cisternae, p210 appears to be a novel protein residing in the cis-Golgi network that may cycle between the Golgi apparatus and the intermediate compartment.
8049572 Neonatal lupus erythematosus: dissolution of atrioventricular block after administration o 1994 Histopathologic and immunofluorescence findings of facial annular erythema on a 3-month-old female child, as well as serological detection of anti-SS-A (Ro) and anti-SS-B (La) antibodies, led to the diagnosis of neonatal lupus erythematosus (LE), while no sign of abnormality in the conducting system of the heart was found. During the pregnancy of the present child her mother, with positive anti-SS-A and anti-SS-B antibodies, had a history of Sweet's syndrome. She was treated with corticosteroid, resulting in a gradual diminution of the existing complete atrioventricular block of the fetus. This history may implicate a potential therapeutic effect for the congenital heart block associated with neonatal LE of corticosteroid given to the pregnant mother.
8346468 [A case of Sjögren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobuline 1993 Jun A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient.
1734495 Clustering of IgA-producing immunocytes related to HLA-DR-positive ducts in normal and inf 1992 Jan Ig-producing immunocytes and epithelial expression of secretory component (SC) and HLA-DR were evaluated by two-colour immunofluorescence staining in 10 normal and 20 inflamed salivary glands; the latter included specimens from 10 patients with obstructive sialadenitis and 10 with Sjögren's syndrome (SS). Epithelium adjacent to T-cell infiltrates showed extensive co-expression of SC and HLA-DR, suggesting that leucocyte-derived cytokines were responsible for this concurrent up-regulation. Clusters (greater than 2 positive cells) of IgA-producing cells were spatially related to DR-positive ducts. The possibility is discussed that DR-expressing epithelium contributes to local terminal differentiation of IgA-producing plasma cells. A cytokine-mediated up-regulation of SC that simultaneously increases the transport capacity for polymeric IgA would constitute an efficient enhancement of secretory immunity in diseased glandular tissue.
1284379 Autoantibodies to the Ro/SSA antigen are conformation dependent. I: Anti-60 kD antibodies 1992 Recent studies have shown that Ro/SSA autoantigen is heterogeneous and the autoanti-Ro/SSA response is correspondingly heterogeneous. There are two isoform families; the 60 kD forms and the 52 kD forms. We studied the antigenic difference between the native and denatured Ro/SSA isoforms and found that the autoanti-Ro/SSA response to the native 60 kD antigen is quite homogeneous. All anti-Ro/SSA sera recognize the native kD antigen regardless of the reactivities to the 60 kD band on the Western blot. Surprisingly, no anti-Ro/SSA sera without anti-La/SSB reacts with the native 52 kD Ro/SSA, although sera with both precipitating anti-Ro/SSA and anti-La/SSB can immunoprecipitate the native 52 kD antigen. Anti-Ro/SSA sera exist which react exclusively with the native 60 kD Ro/SSA protein (10/43, 23%) while no anti-Ro/SSA sera have been found which react exclusively with the denatured 52 kD Ro/SSA antigen. In sera with anti-Ro/SSA precipitins alone, only antibody to the denatured 52 kD Ro/SSA molecule is found! In sera with anti-Ro/SSA and anti-U1 RNP precipitins, no antibody to either native or denatured 52 kD Ro/SSA is found, while in sera with both anti-Ro/SSA and anti-La/SSB precipitins, antibodies to both the native and denatured forms of 52 kD Ro/SSA are present. These data suggest that the anti-Ro/SSA response to the 60 kD molecule is driven by the native 60 kD Ro/SSA molecule while the molecular identification of the antigen drive in the anti-52 kD Ro/SSA response is unknown.
8925658 Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjögren 1996 Mar Our purpose was to evaluate the efficacy of a new formulation of methylcellulose, preservative-free 0.5% hydroxypropyl methylcellulose (HPMC), for the treatment of dry eye. In the clinical part of our study, two groups of dry-eye patients, those with Sjögren's syndrome (SS) and those without (non-SS), were treated topically with 0.5% HPMC and evaluated for symptoms, ocular surface vital staining, tear breakup time (BUT), and tear evaporation rate from the ocular surface at 40% ambient humidity (TEROS40). In the in vivo part of the study, rose bengal uptake was measured in human conjunctival epithelial cells, which were cultured and incubated with or without 0.5% HPMC. Although symptoms improved in both groups, rose bengal and fluorescein staining and BUT improved significantly only in the SS group. TEROS40 increased for 30 min after instillation of 0.5% HPMC, but not after use of 0.1% sodium hyaluronate or saline-based artificial tears. Rose bengal uptake by cultured conjunctival epithelial cells was blocked by 0.5% HPMC. These findings suggest that 0.5% HPMC provides long coverage of and protection for the ocular surface. Patients with severe dry eye, such as in SS, are good candidates for this treatment.
7654659 A cure for xerostomia? Free jejunal patch graft in oral reconstruction. 1995 Jun A case of oral carcinoma associated with extensive leukoplakia and severe xerostomia is presented. The advantage of using a free jejunal patch graft to restore large intra-oral mucosal defects and concurrently eradicate xerostomia is demonstrated. Further, it is recommended that a tracheostomy be used routinely in such cases to avoid postoperative aspiration of the graft secretions. Following healing the use of osseointegrated implants can complete oral rehabilitation without compromising the graft.
7745541 Murine autoimmune exocrinopathy: the minor salivary gland network shows a dichotomous patt 1995 Feb The minor salivary gland network of the MRL/l mouse was investigated in a kinetic study and compared with the major submandibular gland. We report that minor salivary glands adopt two mutually exclusive patterns of inflammatory lesions depending on the gland. The first pattern is characteristic of human Sjogren's syndrome. It developed during the second month, affected 89% of the animals over 20 weeks old, and consisted of an accumulation of mononuclear cells around the duct system. Only the anterior buccal gland (ABG) showed this pattern, which is shared by the major salivary glands. The ratio of CD4+ to CD8+ cells was the same in lesions and in healthy tissue. No neutrophils were found in these lesions. The second pattern affected all the minor salivary glands except the ABG. These lesions were never observed before the age of 20 weeks and affected 38% of MRL/l mice between the ages of 10-32 weeks. In this pattern, neutrophils were frequently found, but mainly gathered at the periphery of the gland lobules. That a systemic immunoregulatory defect may be expressed as two different patterns of histopathology in the minor salivary glands suggest that the network behaves as a dichotomous entity depending on particular microenvironmental influences.
8020554 Infiltrating T cells from patients with primary Sjögren's syndrome express restricted or 1994 Jan Organ-specific autoimmune diseases are usually considered to be mediated by autoreactive T cells which infiltrate the target tissue. Conceivably, these T cells could represent pathogenic autoreactive cells which recognize their specific antigen (peptide or superantigen) within the pathological tissue. Extensive studies dealing with the clonality of the infiltrating autoreactive cells gave conflicting results both in humans and animals. One possibility for explaining these contradictory data could rely on the stage of the disease when the T cell population is studied. Here, we report on this parameter by analyzing T cell receptor beta-chain variable regions of infiltrating T cells involved during one of the most frequent human organ-specific autoimmune disease, the primary Sjögren's syndrome. Six patients were selected on the basis of the duration of the disease before the biopsy procedure (two early and four late stages) to analyze initial and late T cell waves within the abnormal tissue. Using short-term interleukin-2-stimulated T cells, polymerase chain reactions, Southern and sequence analysis, we conclude that: (a) there is a clear restriction in the V beta usage by the infiltrating T cells only during the early stage of the disease, (b) this V beta restriction is related to a monoclonal T cell expansion, (c) the expanded V beta families are different from one patient to the other, and (d) there is no clear homology in length or amino acid composition in the CDR3 of the analyzed V beta regions. These results could provide an explanation to conflicting results on the V beta restriction usage during autoimmune diseases and could indicate time limitations in anti-V beta treatment. Furthermore, the monoclonal expansion of particular V beta-bearing T cells argues against a role for a superantigen during this disease.
8843859 Adherence of synovial cells on EDA-containing fibronectin. 1996 Oct OBJECTIVE: To investigate the role of EDA-containing fibronectin (EDA+ FN), a splice variant of FN detectable in association with cellular transformation, in the adherence of synovial cells (SC) on rheumatoid cartilage surface. METHODS: The number of SC adherent on cartilage slices or on culture plates containing either EDA+ FN or plasma FN (pFN) was enumerated under a phase-contrast microscope. The portion of the FN molecule responsible for adherence of SC onto EDA+ FN was investigated by inhibition studies using antibodies or peptide fragments. RESULTS: SC adhered more strongly on the surfaces containing EDA+ FN than on those containing pFN (P < 0.01). When monoclonal antibodies against the EDA or the carboxyl-terminal heparin-binding (Hep2) domains were used, adhesion of SC onto EDA+ FN was reduced to a level comparable with that onto pFN. FN fragments containing Hep2 or heparan sulfate inhibited the adhesion of SC onto EDA+ FN. Treatment of SC with heparitinase, but not heparinase, reduced the adhesion of SC onto EDA+ FN. CONCLUSION: EDA+ FN enhances adherence of SC on the matrix via the Hep2 region of EDA+ FN.
8793263 Intraarticular minocycline injection in experimental synovitis. 1996 May Minocycline, a semi-synthetic tetracycline, was injected into one hind joint of twenty-two rabbits with zymosan-induced arthritis, while the contralateral joint served as a control. A local inflammatory reaction was observed a few days after the zymosan injection. Most clinical parameters such as knee diameter, systemic temperature, sedimentation rate and blood cell count did not change throughout the experiment both in control and minocycline treated rabbits. However, the zymosan platelet counts rose from 3.4x10(5)/microL to 5x10(5)/microL, as well as the level of serum fibrinogen (from 99 mg% to 370 mg%). Microscopically, a perivascular infiltrate consisting of lymphocytes and polymorphonuclear cells was seen. Lymphoid follicles as well as plasma cells epitheloid and giant cells were also observed. A mild tendency to fibrosis and lesser inflammatory reaction in the minocycline treated knees was noted. Our data suggest that intraarticular minocycline treatment did not alleviate the course of the rheumatoid-like inflammatory reaction of the knee joint.
7863384 [Mixed connective tissue disease in childhood]. 1994 Dec To characterize the clinical features of mixed connective tissue disease (MCTD) in childhood, 23 reported cases in Japan were analyzed for their symptoms and signs, and laboratory data. The earliest onset of the disease was found in 5 years of age, and the number of patients were increased with age. Over 80% of patients was girls. Raynaud's phenomenon preceded in most patients to the increased disease activity manifested by spiky fever, arthritis, skin rashes, and myositis. The characteristic laboratory findings were demonstrated by anti-nuclear antibody (speckled type), anti-RNP antibody, rheumatoid factor, and marked hyper-gammaglobulinemia. The overall prognosis was fairly good. But cardiac involvement was the most serious problem in the early stage of the disease, and a very few children was accompanied with renal disorders. The central nervous system was rarely involved. As the long term follow-up of the children was not accomplished yet, pulmonary fibrosis or pulmonary hypertension was left for the further documentation.
1613697 c-myc mRNA expression in minor salivary glands of patients with Sjögren's syndrome. 1992 May c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells. Sjögren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia. In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry. Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with 35S, were used as probes. To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used. High c-myc mRNA expression was detected on acinar epithelial cells. c-myc did not correlate with c-fos and c-jun protein expression. Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less than or equal to 0.002) and more intense T lymphocyte infiltrates (p less than 0.05) although these patients revealed no hypergammaglobulinemia. No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma. In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS. Our findings may indicate the presence of a reactivated virus hosted in these cells.
28315094 Long-term results of Charnley low friction arthroplasty in patients younger than 40. 1996 Dec We reviewed a consecutive series of 145 total hip arthroplasties that were performed between 1969 and 1983 in 113 patients under 40 years (mean age 33 years). Preoperative diagnosis was secondary osteoarthrosis in 49 hips, rheumatoid arthritis or ankylosing spondylos in 40, avascular osteonecrosis in 38, sequelae of septic arthritis in 6 and others in 12.All operations were performed in a standard operating room. A lateral approach was always used. Cemented implants were Charnley prosthesis (20) before 1973 and Charnley-Kerboull prosthesis (125) from 1973 to 1983.There were 2 delayed unions of the trochanter, 3 deep infections, 1 acute and 2 chronics. Recurrent dislocations due to excessive wear of the acetabular component were observed in 3 hips.At the most recent examination in 1994, 90 hips were reviewed, 48 hips had been lost to follow-up between 6 months and 15 years after surgery, 5 patients (7 hips) had died. The clinical and radiological results of the 137 hips followed up at least 2 years were available for the present study with a median follow-up period of 12 years (range 2 to 24 years). Of these 137 hips, 96 had been followed-up more than 10 years (mean 17 years, range 10 to 24 years).At the latest follow-up, the mean functional score in the d'Aubigné scoring system was 16,5 (range 8 to 18). There were 9 definite and 4 probable loosenings of the socket and 6 definite loosenings of the femoral component (5 subsidences and 1 fracture of the stem). The mean amount of the linear socket wear was 1,62 mm for the 137 hips and 2,22 mm for the 96 hips followed up more than 10 years. Cystic granulomatous lysis was observed in the acetabular area (14 hips), in the calcar (64 hips) and in other zones of the femoral cortex (16 hips). Heterotopic ossification was present in 43 hips.Of the initial 145 hips, 19 had been revised: 3 for septic loosening, 1 for fracture of the stem, 6 for excessive wear of the socket with periacetabular osteolysis and 9 for aseptic loosening (8 acetabular and 1 femoral component). Of these 19 revisions, 11 were performed after 10 years.According to these results the overall probability of retention of the prosthesis was 93,7 at 10 years, 81,5 % at 15 years and 77% at 20 years. When excluding the 3 revisions that were performed for septic loosening, the survival rate was 95,4% at 10 years, 84% at 15 years and 80% at 20 years.These results confirm that the long term reliability of total hip arthroplasty in young patients is less good than in older patients. The main cause of failure was aseptic loosening of the socket which was significantly correlated in this study with an excessive amount of wear. Nevertheless these results performed with a classical friction combination metal on polyethylene are similar or better than other reports with use of new friction combination as alumina-alumina. Further reseach will probably allow us to increase the wear resistance of total hip arthroplasty especially in young patients.Currently, the choices adopted in this series remain a good compromise for us that allow to expect good clinical and radiological results in more than 80% of the cases over 15 years.
8656141 Urolithiasis and distal renal tubular acidosis preceding primary Sjögren's syndrome: a re 1996 Jun OBJECTIVES: Distal renal tubular acidosis (dRTA) can be associated with autoimmune diseases such as primary Sjögren's syndrome (SS). Our objective was to study SS-associated symptoms, autoantibodies and renal histopathology in patients with urolithiasis and dRTA. SETTING: The patients were from the Departments of Nephrology and Rheumatology. University Hospital of Linköping, which is a tertiary referral hospital, as well as a secondary referral centre for the immediate area around the city of Linköping. SUBJECTS: Ten female patients with dRTA, who presented with urolithiasis and not with subjective sicca symptoms, were from the Department of Nephrology, University Hospital, Linköping. Autoantibodies were detected in eight of these patients, and they were studied with respect to clinical and laboratory evidence of SS (urolithiasis group). Fifteen women with SS, who presented with sicca symptoms and not with urolithiasis or dRTA, served as the reference group. RESULTS: In the urolithiasis group, all of the eight patients had anti-SS-A antibodies, and SS (or possible SS) developed in seven of the eight patients 1-48 (mean 15) years after the onset of urolithiasis. Histological features of tubulointerstitial nephritis were found in four of five biopsied patients in the urolithiasis group, and in two of four patients (with dRTA) in the reference group. CONCLUSIONS: Urolithiasis and dRTA can precede subjective sicca symptoms, and patients with dRTA may have SS in the absence of subjective sicca symptoms. Anti-SS-A antibodies are common in patients with urolithiasis and dRTA. Therefore, we hypothesize the possibility of a Sjögren-related renal disease in these patients.
8719354 Biochemical markers of renal disease in primary Sjögren's syndrome. 1995 Dec Primary Sjögren's syndrome (SS) is characterized by an inflammatory process in the salivary and lacrimal glands, but the kidneys may also be involved. Renal tubular functions were studied in 27 patients with SS, all females, age 37-78. Both SS-patients with and without known distal renal tubular acidosis (dRTA) were included, dRTA was found in 18/27 (67%), impaired urine concentrating ability in 13/27 (48%). Hypocitraturia was identified in 20/27 (74%) and reduced tubular reabsorption of phosphate (TRP%) in 18/27 (67%). Tubular proteinuria (alpha 1-mikroglobulin) was present in 11/24 (46%), and tubular enzymuria (NAG) in 7/24 (29%). Hypocitraturia and/or dRTA were found in all patients with any kind of abnormal renal tubular function test. All except one of the patients with dRTA not treated with sodium bicarbonate had hypocitraturia. We conclude that distal tubular dysfunction was common in our SS-patients, but a concommitant proximal dysfunction was also seen. Determination of urinary citrate represents a valuable test for detection of renal disease in SS.
8875745 Antibody to gp39, the ligand for CD40 significantly inhibits the humoral response from Gra 1996 Aug Experimental evidence suggests that interference with gp39-CD40 interactions may have therapeutic potential in prevention of certain autoimmune disorders (i.e., collagen-induced rheumatoid arthritis). The binding between CD40 expressed on mature B cells and CD40 ligand (CD40L, gp39) transiently expressed on activated T helper cells (Th) further stabilizes the interactions (between Th and B cells) and co-ordinates the responses of the interacting cells during antigen presentation, and is essential for thymus-dependent humoral immunity. Graves' disease is the most common form of hyperthyroidism, in which hyperactivity of the thyroid gland is due to an autoantibody directed against the thyrotropin receptor (TSHR). The main objective of our study was to determine the role of interactions between gp39 and CD40 in "an established" human Graves' disease (GD). Severe combined immunodeficient (SCID) mouse served as a vehicle for human Graves' thyroid tissue. This experimental setting allows us to study, observe, and immunomodulate human autoimmune tissue in so called in vivo condition. We studied the effects of ip administration of anti-gp39 mAb on humoral response, thyroid function tests, expression of adhesion molecules, and HLA-DR on human thyrocytes and histopathological changes from human GD thyroid tissue xenografts. GD thyroid tissue from 4 patients was xenografted into 20 SCID mice (0.8 g/mouse). Human immunoglobulin G (IgG) levels became detectable in SCID mice 1 week after xenograftment. Ten SCID mice were sequentially administered anti-gp39 mAb (250 micrograms/mouse/ dose) ip every 4 days until the end of the experiment. Ten control animals were injected with vehicle (PBS) in similar fashion. Blood samples were taken every 2 weeks from the tail veins for measurement of the humoral response [human IgG, thyroid-stimulating antibody (TSAb), antithyroperoxidase (anti-TPO), and antithyroglobulin (anti-Tg), Abs], and thyroid function tests. After 8 weeks, animals were sacrificed and thyroid tissue was examined histologically. The humoral response from the intrathyroidal lymphocytes was measured and the tissue morphology of GD was preserved during the 8-week period in phosphate-buffered saline (PBS)-treated SCID mice xenografted with GD xenografts. However, administration of anti-gp39 mAb completely blocked or significantly decreased the humoral response in all treated animals. On the other hand, no significant histological changes were associated with the administration of anti-gp39 mAb. The degree of lymphocytic infiltration in thyroid tissue xenografts was comparable in both groups. Serum thyroxine values were normal in both groups. In spite of a profound immunosuppressive effect on the humoral response by directly blocking CD40-gp39 interactions in vivo, this did not result in complete deletion of the responding Th in the thyroid specimens.