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G Riethmüller

Publications and source records attributed to G Riethmüller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Reduction of metastatic carcinoma cells in bone marrow by intravenously administered monoclonal antibody: towards a novel surrogate test to monitor adjuvant therapies of solid tumours.

In a pilot, prospective randomised study, 40 patients with breast and colorectal cancer presenting with metastatic cytokeratin (CK)-positive tumour cells in bone marrow were treated either with six doses of 100 mg of a monoclonal Lewis Y antibody during 2 weeks or with a placebo regimen, consisting of six infusions of human serum albumin (HSA). CK-positive cells in marrow were monitored prior to and on days 15 and 60 after commencement of treatment. In 30 patients presenting with relatively low tumour cell numbers (1-11 per 4 x 10(5) bone marrow cells), a therapy-induced reduction of CK-positive cells could not be conclusively determined. More meaningful quantitative data were obtained in 10 breast cancer patients presenting with more than 20 tumour cells per 4 x 10(5) nucleated bone marrow cells. 7 of these patients had been randomised to the antibody arm, and 5 showed an eradication or a distinct reduction of CK-positive/Lewis Y-positive cells of at least one log unit, while 2 patients, presenting with Lewis Y-negative tumour cells, showed no corresponding decrease. Similarly, in all 3 patients randomised to the placebo arm, tumour cells were not reduced. Because the antibody exerted a marked cytotoxicity on tumour cell lines when tested ex vivo in serum taken from these patients after antibody infusion, we postulate that the observed, prompt reduction of individual tumour cells in bone marrow was due to the cytotoxic action of the injected antibody. Although monitoring micrometastatic cells in bone marrow of patients with high tumour cell counts appears to be feasible, the immunocytochemical assay needs to be improved for patients with lower cell numbers before it can be applied as a surrogate test for adjuvant therapies.

Antibodies, Monoclonal↗
PubMed1995

Immunocytologic detection of isolated tumor cells in bone marrow of patients with squamous cell carcinomas of the head and neck region.

The well-documented specificity of anticytokeratin monoclonal antibodies for detection of epithelial micrometastatic cancer cells in bone marrow as a prognostic indicator inspired us to apply this approach to patients with squamous cell carcinomas (SSC) of the head and neck region. The sensitivity of the broad-spectrum anticytokeratin monoclonal antibody (mAb) A45-B/B3 used for tumor cell detection was demonstrated by immunostaining of cryostat sections from the respective primary tumors. Analysis of 31 patients with SSC revealed A45-B/B3-positive cells in 10 cases (32.3%) at frequencies of 1-207 per 1 x 10(6) mononuclear cells. Most specimens displayed isolated tumor cells, while cell clusters were found in only two cases (6.5%). The present data suggest that hematogenous dissemination of cancer cells is more frequent than expected from clinicopathologic staging of patients with SSC of the head and neck region.

Adult↗
PubMed1995

Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection.

In acute and chronic viral disease the specific response of CD4+ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4+ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Fas/Apo-1 activates nuclear factor kappa B and induces interleukin-6 production.

Fas antigen/Apo-1 (Fas) and the p55 tumor necrosis factor receptor (TNF-R) are two related cell surface molecules that induce apoptosis in susceptible cells. With regard to their cytoplasmic homology region, we investigated whether Fas like the TNF-R activates nuclear factor kappa B (NF-kappa B), using human SV80 fibroblasts transfected with the cDNA encoding human Fas. In this cell line Fas mobilizes the p50/p65 heterodimeric form of NF-kappa B and induces interleukin-6 (IL-6) production. Compared to NF-kappa B activation via the TNF-R differences in kinetics and signal intensity were observed. Peak activation occurred 2 hr after Fas compared to 1 hr after TNF-R stimulation. Furthermore, when equitoxic concentrations of anti-Fas antibody and TNF were applied, TNF triggered a stronger NF-kappa B response. Studies using inhibitors of signal transduction suggest that both receptors mediate NF-kappa B activation via similar routes: D609, an inhibitor of the phospatidylcholine-specific phospholipase C, had an inhibitory effect, while the protein kinase C inhibitor staurosporine had an enhancing effect on both Fas and TNF-R induced NF-kappa B mobilization. Interestingly, D609 had no influence on Fas and TNF-R mediated cytotoxicity arguing against an involvement of NF-kappa B in the cell death pathway triggered by these receptors. This is the first indication that Fas may activate genes via NF-kappa B and may thus in addition to its role as a cell death inducing receptor serve a much broader range of biological functions.

Antibodies↗
PubMed1995

ICAM-1 expression on alveolar macrophages and in serum of sarcoidosis patients.

The intercellular adhesion molecule-1 (ICAM-1) is important in mediating intercellular contact in inflammation. Therefore, we have analyzed the expression of this molecule on alveolar macrophages (AM) and in serum of patients with sarcoidosis. Bronchoalveolar lavage (BAL) cells from 13 patients and 11 control donors were stained with an anti ICAM-1 monoclonal antibody (mAb) or an isotype control. Alkaline phosphatase was used as a detection system, followed by digital single cell image analysis. Soluble ICAM-1 in serum (ssICAM-1) was determined by enzyme linked immunoassay (Elisa). Immunocytochemistry revealed a strong increase of ICAM-1 expression on AM from sarcoidosis patients (64%) compared to healthy controls (30%). Furthermore, patients exhibited a fourfold higher antigen density. Serum levels of sICAM-1 were more than twofold increased in the patient group (805.4 micrograms/ml) compared to healthy controls (384.8 micrograms/ml). SsICAM-1 showed an inverse correlation with vital capacity (VC) and diffusing capacity (DCO). This significant correlation with impairment of two important lung function parameters suggests that ssICAM-1 might be useful in serological assessment of disease activity in sarcoidosis.

Adult↗
PubMed1994

Characteristics of carcinoembryonic antigen (CEA) expressed in different cell types: evidence that CEA can function as an adhesion molecule and as a repulsion molecule.

The characteristics of carcinoembryonic antigen (CEA) molecules expressed by different cell types have been examined using cDNA transfection into cells of epithelial, neuroectodermal and hematopoietic origin. Variability in the CEA molecules was observed in terms of monoclonal antibody binding, apparent molecular weight and sialic acid content, although this was not cell type specific. CEA was found to mediate homotypic as well as heterotypic intercellular adhesion independently of the cell type and despite differences in the sialic acid content. Although CEA was shown to function as a homophilic cell adhesion molecule in most cells, expression of CEA in one cell line led to a reduction in both homotypic and heterotypic cell adhesion, suggesting that it can under certain circumstances also function as a repulsion molecule.

Animals↗
PubMed1994

MUC18, a melanoma-progression associated molecule, and its potential role in tumor vascularization and hematogenous spread.

The MUC18 protein, a member of the immunoglobulin superfamily and related to several adhesion molecules, shows an expression pattern in human malignant melanoma which is closely associated with tumor progression and the onset of metastasis. To determine the expression pattern of MUC18 in normal human tissues, immunohistochemical analysis was performed on frozen sections of a variety of normal human tissues using monoclonal antibodies against three different epitopes. This analysis showed that expression of MUC18 is limited to smooth muscle cells and to vascular endothelium. No reactivity could be observed with epithelial cells or with quiescent or activated hemopoetic cells. Smooth muscle cells in lung, skin, and in the gastrointestinal tract express MUC18 as does vascular smooth muscle, whereas myocardium or skeletal muscle appeared negative. Comparison of MUC18 staining with that of the panendothelial marker CD31 showed that MUC18 is expressed on the endothelia of a subset of blood capillaries and in tumor vessels but is absent on the endothelium of arterial vessels and large veins. The regulation of MUC18 expression was investigated in vascular smooth muscle cells and endothelial cells cultured in vitro. These studies revealed induction of the gene in endothelial cells upon proliferation. The observation that the MUC18 protein is not only present on melanoma cells but also on the endothelia of blood vessels penetrating primary and metastatic melanomas suggests a complex involvement of this potential cell adhesion molecule in tumor angiogenesis and metastasis.

Antigens, CD↗
PubMed1994

Chimeric monoclonal CD4 antibody--a novel immunosuppressant for clinical heart transplantation.

The murine CD4 monoclonal antibody (mAb) M-T412 effectively downregulates T-helper-inducer function, while exhibiting high affinity and specificity for an epitope formed by the V1 and V2 domain of CD4. The antibody was chimerized by combining the murine VH and VL parts to the constant region of a human IgG1 kappa immunoglobulin. This chimeric CD4 monoclonal antibody (chim CD4 mAb) cM-T412 was used for adjunct immunosuppression in addition to standard triple-drug therapy for patients after orthotopic (n = 10) and heterotopic (n = 1) heart transplantation (HTx). cM-T412 was administered intraoperatively and postoperatively on days 1-7, 9, 11, 13, 17, and 21. A control group of similar composition (10 orthotopic, 1 heterotopic HTx) was conventionally treated in an adjunct fashion with antithymocyte globulin (ATG) until cyclosporine (CsA) in serum had reached therapeutic levels. Over the total observation time (mean: 600 days), the number of acute rejection episodes per 100 patient days was 0.26 in the cM-T412 group versus 0.41 in the control group, indicating a reduction of nearly 40%. Four of the 11 patients in the CD4 group have thus far not experienced any rejection crisis compared with two out of 11 in the control group. The mean time to the first rejection episode was 43.7 days in the CD4-treated patients versus 25.3 days in the control group. In addition the interval to the second rejection episode was longer in CD4 patients than in controls. Furthermore, patients treated with chim CD4 mAb had fewer episodes of infection during the first year after HTx (0.49 vs. 0.91 per 100 pt. days) and had a better overall survival rate (91% vs. 73%) than control group pts. No anaphylactic reaction was observed. The only adverse event probably related to cM-T412 infusion was a transient decrease of blood pressure in one patient. Although this study has only a limited number of patients, addition of cM-T412 to standard triple drug therapy appears to be an effective, specific, and well tolerated adjunct to current immunosuppression that offers a new approach for an improved immunomodulatory regimen after heart transplantation.

Adult↗
PubMed1994

Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers.

Stimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide (LPS) leads to rapid and transient expression of cytokines like tumor necrosis factor (TNF). When such cells are precultured for 2 days with a low dose of LPS (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml), expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear run-on analysis, such tolerant cells show only a low degree of transcription, indicating that tolerance operates at or upstream of the transcription level. The CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant cells, and LPS can, in fact, still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B (NF-kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50-p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of a transcriptional up-regulation of p50. Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when precultured with a low dose of LPS, also become tolerant and produce little TNF after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together, these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex.

Antigens, CD↗
PubMed1994

Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Antibodies, Monoclonal↗
PubMed1994

Deletion of T lymphocytes in human CD4 transgenic mice induced by HIV-gp120 and gp120-specific antibodies from AIDS patients.

CD4, a T cell receptor for major histocompatibility complex class II antigen, is a key regulator of immunological reactivities. When engaged together with the T cell antigen receptor, CD4 enhances immune reactions, whereas when ligated independently of the antigen receptor CD4 inhibits the activation of T cells or initiates their deletion. CD4 serves also as a receptor for the human immunodeficiency virus (HIV), which binds the receptor with high avidity through its envelope molecule, gp120. Studies in tissue culture have shown that its affinity to CD4 gives the virus opportunities to utilize CD4-mediated signaling and to manipulate immunocytes. We show here in human CD4 transgenic mice that appropriately cross-linked HIV envelope protein causes massive deletion of HIV-reactive T cells in vivo.

Animals↗
PubMed1994

Detection of autoantibodies against M2, LKM-1, and SLA in liver diseases by standardized uniform ELISA-techniques.

Antibodies directed against soluble liver antigen (SLA), liver kidney microsomal antigen (LKM-1-AG), and antimitochondrial antigen M2 (M2-AMA) are critical serological markers for the differential diagnosis of autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). The exact diagnosis of autoimmune hepatitis and PBC is of great clinical relevance, as it leads to different therapeutic strategies. In the present work, a simple and reliable ELISA test system is described, which applies the same test principle for the detection of three different species of autoantibodies important for the diagnosis of chronic liver disease. The ELISA assays are based on a competitive inhibition of binding of positive standard antibodies by patients sera containing antibodies of unknown specificity. The purified immunoglobulins of clinically and serologically clearly defined patients with SLA or LKM-1 positive AI-CAH and with M2 positive PBC were used as coating- and detection antibodies in the ELISAs. From homogenized rat liver the fractionated 100,000g supernatant was employed for the SLA ELISA, the microsomal preparation served as antigen for the LKM-1 ELISA and the mitochondrial preparation was used for the M2 ELISA. In 1,500 sera of patients with the differential diagnosis of a hepatobiliary disease, 17 gave a positive signal in the SLA-ELISA, 12 in the LKM-1-ELISA, and 72 in the M2-ELISA. The results of the ELISAs were compared with Western blotting and immunofluorescence staining pattern on cryostat sections and Hep2 cells. The antibody profiles of several patients are described in detail.

Adult↗
PubMed1994

Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer.

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+ cells were detected in a sensitivity of 1 per 8 x 10(5) marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+ tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+ cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by gold-conjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Diseases↗
PubMed1994

Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow.

The emerging clinical relevance of bone marrow micrometastasis has prompted several investigations, using a variety of immunocytochemical approaches. The present study was designed to evaluate some of the variables affecting the immunocytochemical detection of individual epithelial tumor cells in bone marrow. Using an alkaline phosphatase-antialkaline phosphatase staining technique, we evaluated bone marrow aspirates from 358 patients with primary carcinomas of the breast (n = 150), lung (n = 66), prostate (n = 42), or colorectum (n = 100). Individual tumor cells in cytological preparations were detected with monoclonal antibody (MAb) CK2 to the epithelial cytokeratin component 18 (CK18), which has been validated in extensive clinical studies. In addition, the utility of the broad-spectrum MAb A45-B/B3 was explored in this study. The high specificity of MAbs CK2 and A45-B/B3 was supported by analysis of bone marrow from 75 noncarcinoma control patients and by double-marker analysis with MAbs to mesenchymal marker proteins (CD45 and vimentin). In contrast, MAbs E29 and HMFG1, directed to mucin-like epithelial membrane proteins, cross-reacted with hematopoietic cells in 26.7-42.7% of all samples tested. The majority of the 154 positive samples (43.0%) from cancer patients displayed less than 10 CK18-positive cells per 8 x 10(5) marrow cells analyzed. The detection rate, however, was affected by blood contamination of the aspirate, the number of aspirates analyzed, and the number of marrow cells screened per aspiration site. Comparative immunostaining of bone marrow specimens with MAbs CK2 and A45-B/B3 indicated that downregulation of CK18 in micrometastatic carcinoma cells occurs in about 50% of the 172 samples analyzed, regardless of the primary tumor origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1994

Treatment of rheumatoid arthritis with a chimeric CD4 monoclonal antibody (cM-T412): immunopharmacological aspects and mechanisms of action.

To investigate the mechanisms of action underlying the therapeutic effect of CD4 monoclonal antibody therapy in rheumatoid arthritis (RA), clinical responses were compared with several laboratory parameters. Twenty-nine RA patients received either 10 mg, 50 mg or 100 mg of cM-T412, a chimeric CD4 MoAb, for 7 days. The CD4 binding sites on circulating lymphocytes were saturated directly with cM-T412 and serum levels of unbound cM-T412 accumulated towards day 7 of treatment only in the patients treated with 50 and 100 mg. The treatment induced an instant and prolonged depression of the number of circulating CD4+ cells, similar for all dosages. Clinical improvement was observed predominantly in the patients treated with 50 or 100 mg cM-T412 daily and did not correlate with changes in counts of circulating leucocyte subsets nor with changes in serum cytokine levels. An antiglobulin response against cM-T412 developed in a majority of the patients. Side effects on the first day of treatment were correlated with an increase of serum IL-6 levels. This study indicates that a favourable clinical effect of cM-T412 administration was associated with the presence of unbound cM-T412 in the circulation of RA patients. Therefore penetration of unbound cM-T412 into the site of inflammation might determine the therapeutic effect in RA.

Adult↗
PubMed1994

Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer.

PURPOSE: This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). METHODS: Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells. RESULTS: Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005). CONCLUSION: Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Treatment of myasthenia gravis with anti-CD4 antibody: improvement correlates to decreased T-cell autoreactivity.

We treated a patient with severe myasthenia gravis with a chimeric (murine/human) anti-CD4 monoclonal antibody (cM-T412) for 7 days and followed the therapeutic effect by standardized muscle function tests, single-fiber electromyography, and immunologic examinations of disease-specific B- and T-cell functions. Clinical and electrophysiologic improvement began within 4 days, lasted for 3 months, and was maximal between days 16 and 58. The CD4+ lymphocytes decreased to a minimum of 80 cells per microliters of peripheral blood, recovered slowly during the first year of follow-up, and did not correlate with changes in disease severity. T-cell stimulation by human acetylcholine receptor was abolished by the treatment but became detectable at the time of worsening of symptoms. The concentration of acetylcholine receptor antibodies in serum was not decreased by the treatment. The results suggest that anti-CD4 antibody administration could be effective in the treatment of severe myasthenia gravis and indicate that acetylcholine receptor-specific T lymphocytes might contribute to the disturbed neuromuscular transmission in the disease.

Antibodies↗