Intravenous immunoglobulins may prevent prednisone-exacerbation in myasthenia gravis.

Corticosteroids may produce a paradoxical worsening of myasthenia gravis (MG) symptoms within the first weeks of treatment. We therefore wanted to assess the hypothesis that a prior infusion of intravenous immunoglobulin (IVIG) may have a protective effect. Our primary objectives were to show that the coadministration of immunoglobulins and glucocorticoids is safe and effective for controlling myasthenic symptoms, and to compare the exacerbation rate with this approach and historical practice without IVIG. We recruited 45 patients with generalized MG who required corticosteroids for the first time and we gave all IVIG before starting the full doses of prednisone. Monitoring was performed with validated scales, questionnaires, and blood tests over a 6-week period. Only 4.4% had severe adverse effects related to IVIG and 86.7% improved clinically. Notably, only 2.2% had a paradoxical symptom exacerbation in the first weeks of starting prednisone, which was statistically lower than the 42% reported in a historical series. We conclude that adjuvant therapy with IVIG when starting prednisone for the first time in patients with generalized MG is safe and effective. Given that the rate of paradoxical worsening was lower than that previously reported, the addition of IVIG may have a protective effect against such exacerbations.

Prevalencia de miastenia gravis en la comarca de Osona (Barcelona, Cataluña) / Prevalence of myasthenia gravis in the Catalan county of Osona

INTRODUCCIÓN: La prevalencia descrita de miastenia gravis (MG) oscila entre 5 y 24 casos por 100.000, representando los mayores de 65 años menos del 50% del total. Se presenta la prevalencia de MG en la comarca de Osona (Barcelona, España). Se describen la prevalencia y las características clínicas por grupos de edad, diferenciando los menores y mayores de 65 años. MÉTODOS: El Servicio de Neurología del Hospital General de Vic puso en marcha en el año 1991 un registro comarcal sobre los casos de MG diagnosticados. RESULTADOS: La prevalencia de MG fue de 32,89 × 105 habitantes (IC 95%, 23,86-41,91). La prevalencia estandarizada (población europea) fue del 35,47×105 habitantes (IC 95%, 26,10-44,84). La razón por sexo, mujeres/hombres, es de 1,3. De forma global, el grupo de más de 65 años representa el 62,75% de los casos. Las prevalencias de MG por grandes grupos de edad presentan un carácter marcadamente ascendente, pasando de ningún caso en el grupo de menos de 25 años, a 21,87 × 105 en el grupo de 25 a 64 años, alcanzando 122,35×105 en el grupo de 65 y más años. Las clínicas pretratamiento y a fecha de corte no presentan diferencias estadísticamente significativas (p > 0,05) entre menores y mayores de 65 años. CONCLUSIONES: Se describe la prevalencia más alta comunicada hasta la actualidad. Esta alta prevalencia es a expensas del grupo de más de 65 años. Estos resultados son una nueva alerta para evitar el infradiagnóstico de la MG en el anciano

INTRODUCTION: The reported prevalence of myasthenia gravis ranges between 5 and 24 cases per 100,000, and people over 65 years account for less than 50% of all cases. The prevalence and clinical characteristics of myasthenia gravis in the county of Osona were studied in patients younger and older than 65. METHODS: The study draws from the county-based prospective myasthenia gravis register implemented by the Neurology Department at Hospital General de Vic in 1991. RESULTS: The prevalence of myasthenia gravis was 32.89 × 105 inhabitants (95% CI, 23.86-41.91). The standardized prevalence (European population) was 35.47 × 105 inhabitants (95% CI, 26.10-44.84). The ratio of women to men was 1.3. Overall, the group of patients older than 65 accounted for 62.75% of all cases. The prevalence of myasthenia gravis increased considerably in older age groups. No cases were registered among patients under 25 years old, prevalence was 21.87 × 105 in the 25 to 64 age group, and prevalence in patients over 65 years increased to 122.35×105. The clinical characteristics prior to treatment and at the cut-off date are similar (P > .05) in patients younger than 65 and those aged 65 and older. CONCLUSIONS: These figures show the highest prevalence rate reported to date. This high prevalence is due to the rate observed among patients older than 65. These results provide a new warning that myasthenia gravis may be underdiagnosed in the elderly populatio

Extracorporeal photopheresis did not prevent the development of an autoimmune disease: myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a neuromuscular disorder characterized by an autoimmune defect in the neuromuscular junction. In most patients, the autoimmune attack is mediated by antibodies against the acetylcholine receptor (AChR) on the postsynaptic membrane. Deficient immunoregulation, including regulatory T cells, is consistently observed. Extracorporeal photopheresis (ECP) leads to the induction of regulatory T cells that mediate immunologic tolerance in autoimmune diseases; however, the data regarding MG are very limited. CASE REPORT: Here, we report a patient who, during ongoing ECP therapy for his severe, refractory, chronic graft-versus-host disease (cGVHD), developed MG, although he responded very well to ECP, as indicated by the lowering of his chronic cGVHD severity grade to moderate. RESULTS: Despite receiving ECP, our patient developed MG, which was resistant to treatment and required intensive care unit support. CONCLUSIONS: Close surveillance is required when ECP is planned as one of the treatment alternatives in myasthenia gravis that develop in cGVHD.

Research on the influence of α-GalCer activating experimental autoimmune myasthenia gravis mice NKT cells at different times on myasthenia gravis.

This study aims to observe the effect of natural killer T (NKT) cell activation on experimental autoimmune myasthenia gravis (EAMG) model by injecting mice with α-GalCer in enterocoelia at different times, thus to provide a new therapy for EAMG. EAMG animal model of C57BL/6 mice was established and the mice were injected with α-GalCer irritant in enterocoelia. Vα14 NKT NKT cells were then activated through the transfer of CD1d. This paper discusses the effect of NKT cell activation on EAMG at different times by observing the variation of weight, clinical performance and relevant immunity indexes of mice. In C57BL/6 mice, the EAMG incidence rate of the Vehicle Group was 90%, the average onset duration was 37 ± 6 days; The incidence rate of α-GalCer prevention group was 30%;, the average onset duration was 51 ± 9 days. The forward immunization of α-GalCer activates NKT and protects C57BL/6 mice from the occurrence of EAMG, which provides basis for prevention and treatment of EAMG and other autoimmune diseases.

Debut de miastenia gravis en atención primaria. A propósito de un caso / Onset of myasthenia gravis in primary care. Presentation of a case

La miastenia gravis es un trastorno de carácter autoinmune, de la transmisión neuromuscular que involucra la producción de autoanticuerpos dirigidos contra receptores músculo-esqueléticos, en la gran mayoría de los casos de acetilcolina. Clínicamente se caracteriza por la aparición de debilidad muscular tras una actividad prolongada, que tiende a la recuperación tras un periodo de descanso o con la administración de fármacos anticolinesterásicos. Es una enfermedad relativamente poco común, aunque la prevalencia ha aumentado por la mejoría en el diagnóstico y aumento de la longevidad de la población. El diagnóstico puede apoyarse tras su sospecha en pruebas farmacológicas, inmunológicas o en electrofisiología. El tratamiento puede dividirse en: sintomático, tratamiento a corto plazo y a largo plazo. Presentamos el caso clínico de una paciente que acude a consulta con la única clínica de diplopia, siendo esta debilidad muscular el síntoma inicial más común de la enfermedad (AU)

Myasthenia gravis is an autoimmune disorder of neuromuscular transmission involving the production of autoantibodies directed against skeletal muscle receptors, in most cases of acetylcholine. Clinically it is characterized by the appearance of muscle weakness after prolonged activity, which tends to recover after a period of rest, or administration of acetylcholinesterase inhibitors. It is a relatively rare disease, although the prevalence has increased by improved diagnosis and increased longevity of the population. The diagnosis can be based on evidence after it is suspected using pharmacological, immunological or electrophysiology tests. Treatment can be divided into: symptomatic, short term and long term. We report the case of a patient who complained of diplopia, this muscle weakness being the most common initial symptom of the disease (AU)

Myasthenia gravis appearing after thymectomy.

We aimed to evaluate the clinical characteristics of patients with postoperative myasthenia gravis (MG). We retrospectively studied the data of 174 thymoma patients treated between 1990 and 2008 in Xiangya Hospital. Six of 125 patients without preoperative MG (4.8%) developed postoperative MG. The anti-acetylcholine-receptor binding antibody (ARAb) titers were elevated preoperatively in 22 of the 125 patients (17.6%) who did not have preoperative MG (range, 0.5-67.6nmol/L). Four of six patients with postoperative MG had positive ARAb levels preoperatively. Serum titers were exacerbated in all six patients at the onset of postoperative MG. Postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. We concluded that a thymectomy did not prevent postoperative MG. Exacerbated ARAb levels after thymectomy suggested an extrathymic production of ARAb. We suggest that a rise in the ARAb titer might be a risk indictor for post-thymectomy MG.

Preoperative steroid therapy stabilizes postoperative respiratory conditions in myasthenia gravis.

OBJECTIVE: We reviewed our experience from 1990 to 2005 to examine whether control of myasthenia gravis (MG) with steroid therapy before surgery could stabilize postoperative respiratory conditions, compared with the nonsteroid treatment. METHODS: Records of 43 consecutive patients with MG who underwent extended thymectomy at Kansai Medical University Hospital were retrospectively reviewed. Two groups, a steroid group (n = 28) and a nonsteroid group (n = 15) were compared. RESULTS: In the steroid group, steroid doses ranged from 10 to 100 mg every other day, or 40-60 mg daily. The patients showed significantly less thymus hyperplasia in the pathological findings (P = 0.023). Whereas 3 of 28 (7%) in the steroid group suffered respiratory insufficiency within 3 days of surgery, 5 of 15 (33%) in the nonsteroid group exhibited the same problem (P = 0.030). Univariate analysis showed that steroid treatment was the only significant factor (P = 0.041) affecting respiratory insufficiency. Patients in the steroid group achieved palliation of MG more quickly after surgery than patients in the nonsteroid group (86% vs. 57% within 6 months, P = 0.059; 84% vs. 42% within 1 year, P = 0.042). CONCLUSION: The control of myasthenia gravis with steroid therapy before surgery seems to stabilize postoperative respiratory status without having adverse effects on surgical infection.

Prospects for a T-cell receptor vaccination against myasthenia gravis.

T-cell receptor (TCR) vaccination has been proposed as a specific therapy against autoimmune diseases. It is already used in clinical trials, which are supported by pharmaceutical companies for the treatment of multiple sclerosis, rheumatoid arthritis and psoriasis. Current vaccine developments are focusing on enhancement of immunogenicity as well as selecting the best route of immunization and adjuvant to favor the therapeutic effect. In the meantime, academic laboratories are tackling the regulatory mechanisms involved in the beneficial effect of the vaccines to further understand how to control the therapeutic tool. Indeed, several examples in experimental models of autoimmune diseases indicate that any specific therapy may rely on a delicate balance between the pathogenic and regulatory mechanisms. This review presents a critical analysis of the potential of such therapy in myasthenia gravis, a prototype antibody-mediated disease. Indeed, a specific pathogenic T-cell target population and a TCR-specific regulatory mechanism mediated by anti-TCR antibodies and involved in protection from the disease have recently been identified in a patient subgroup. The presence of spontaneous anti-TCR antibodies directed against the pathogenic T-cells that may be boosted by a TCR vaccine provides a rationale for such therapy in myasthenia gravis. The development of this vaccine may well benefit from experience gained in the other autoimmune diseases in which clinical trials are ongoing.

Myasthenia gravis appearing after thymectomy for thymoma.

OBJECTIVE: A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. METHODS: We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. RESULTS: Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. CONCLUSIONS: Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.

[Mechanism of cellular immunity accommodation in prophylactic effects of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in Lewis rats].

OBJECTIVE: To study the mechanism of prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG). METHODS: Clinical and immunological changes were observed in Lewis rats administered with dual analogue Lys262-Ala207 nasally, to compare the effects between the rats with predetermined dosage of Lys262-Ala207 and control peptides at two different time points, before the day (Group A or C) or on the day (Group B or D) of immunization with acetylcholine receptor (AChR) in complete Freud's adjuvant for 10 consecutive days. The clinical scores was evaluated for 50 days post immunization. Numbers of MNC expressing IFN-gamma, IL-4 or IL-10 and CD4+ and/or CD25+ from lymph nodes were enumerated by flow cytometry. Proliferative response, expressed as stimulation index (SI), was suppressed in response to antigen-specific stimulation in the rats receiving dual analogue, as compared with the rats receiving saline buffer only. RESULTS: Group A and group B of Lewis rats developed EAMG with reduced severity, as compared to the control groups. Number of cells synthesizing IFN-gamma, IL-4 or IL-10 decreased, whereas numbers of CD4+CD25+ cells increased in group A and B than those in the control groups. Proliferative response was suppressed in response to antigen-specific stimulations in the rats receiving dual analogue Lys262-Ala207. CONCLUSIONS: Nasal administration with a dual analogue Lys262-Ala207 at two different time points, before the day and on the day of immunization, could delay symptoms of muscular weakness in EAMG rats, which was associated with suppression of immune function in AChR antigen-specific T cells and lay a scientific foundation for treatment of human MG with nasal dual analogue.

The effect of prednisone on the progression from ocular to generalized myasthenia gravis.

Fifty percent of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia, 90% within 3 years from the onset of ocular symptoms. This study was performed to determine whether treatment with oral prednisone initiated and completed within 2 years from the onset of ocular symptoms would affect the progression of ocular myasthenia to generalized myasthenia gravis (GMG). Fifty-six patients were included in this review, with 27 patients in the prednisone-treated group and 29 patients in the untreated group. The treated group was initiated on 60 mg of prednisone daily with a slow taper over 3-6 months. At 2 years, significantly fewer patients in the treated group (3 of 27) progressed to generalized myasthenia when compared to the untreated group (10 of 29) (chi(2), p=0.04). Our results suggest that the early use of steroids may decrease progression of ocular to generalized myasthenia gravis. The decision to use steroids should be considered early in the course of patients diagnosed with ocular myasthenia gravis. This study should be considered preliminary and a prospective trial is warranted to confirm our observations.

[Sarcoidosis, myasthenia gravis and anterior ischaemic optic neuropathy: severe side effects of adjuvant interferon-alpha-therapy in malignant melanoma?]. / System-sarkoidose, Myasthenia gravis und anteriore ischämische Optikusneuropathie: schwere Nebenwirkungen unter adjuvanter Interferon-alpha-Therapie bei malignem Melanom?

In dermato-oncology, interferon-alpha is widely used as treatment of cutaneous lymphoma and as adjuvant therapy in high risk malignant melanoma. With increasingly wide administration of interferon-alpha (IFN-alpha), not only early-onset side effects, such as influenza-like symptoms, but also uncommon late-onset side effects are being recognized. We present three patients with melanoma who developed rare side effects in the course of adjuvant IFN-alpha-therapy: sarcoidosis, myasthenia gravis and anterior ischaemic optic neuropathy. Based on current knowledge a causal relationship between these diseases and the administration of IFN-alpha can neither be affirmed or absolutely ruled out. Therefore special attention should be paid to such coincidences.

On the initial trigger of myasthenia gravis and suppression of the disease by antibodies against the MHC peptide region involved in the presentation of a pathogenic T-cell epitope.

Myasthenia gravis (MG) is a disabling autoimmune disease caused by autoantibodies (auto-Abs) against the self-acetylcholine receptor (AChR). Although a great deal of information is known about the molecular and cellular parameters of the disease, its initial trigger, however, is not known. To study the possibility of the involvement of microbial antigens that mimic AChR in triggering MG, we have searched the microbial proteins in the data bank for regions that are similar in structure to the regions of human (h) AChR alpha chain recognized by auto-Abs in MG patients. Hundreds of candidate structures on a large number of bacterial and viral proteins were identified. To test the feasibility of the idea, we synthesized four microbial regions similar to each of the major autodeterminants of hAChR (alpha12-27, alpha111-126, alpha122-138, alpha182-198) and investigated their ability to bind auto-Abs in MG and normal sera controls. It was found that MG sera potentially recognized a significant number of these microbial regions. The results indicate that in some MG cases, immune responses to microbial antigens may cross-react with self-antigen (in this case hAChR) and could constitute initial triggers of the disease. Although anti-AChR Abs directly contribute to the degradation of AChR at the neuromuscular junctions, autoreactive T cells provide help to B cells that synthesize anti-AChR auto-Abs. To cause MG, T cells must recognize the pathogenic epitopes in the context of MHC class II molecules related to MG. The ability to regulate AChR presentation (hence AChR-reactive T-cell activation) could form the basis of an effective strategy for the control of autoimmunity in MG by selectively inhibiting the function of the Ir gene loci linked to disease susceptibility. An animal model of MG (experimental autoimmune MG, EAMG) can be induced in C57BL/6 (B6, H-2b) mice by immunization with Torpedo californica (t) AChR. A mutant mouse of B6, B6.C-H-2bm12 (bm12), which has three amino acid changes (at residues 67, 70, and 71) in the I-A beta(b) subunit, is resistant to EAMG development. Recently, we showed that region 62-76 of I-A beta(b), which contains the above residues, is involved in the binding to a pathogenic T-cell epitope within peptide t alpha146-162. We have prepared several monoclonal antibodies (mAbs) against peptide I-A beta(b)62-76, which are highly cross-reactive with I-A(b) molecules. These mAbs inhibited in vitro the proliferation of disease-related T cells of B6 specific to tAChR peptide t alpha146-162. Passive transfer of these mAbs suppressed the occurrence of clinical EAMG, which was accompanied by lower T-cell and Ab responses to tAChR. The results indicated that blocking disease-related MHC by targeting a disease-associated region on MHC molecules could be an effective, straightforward, and feasible strategy for immunointervention in MG.

Timectomía en la miastenia gravis: evolución a largo plazo y factores pronósticos / thymectomy in myasthenia gravis: long-term evolution and predictive factors

Introduction. Thymectomy is a surgical procedure which is generally accepted for treatment of myasthenia gravis. Objective. To describe the long-term evolution of 217 myasthenic patients who had had thymectomies in the Hospital Clinico Quirurgico Hermanos Ameijeiras in La Habana, Cuba. Patients and methods. We determined the stage of evolution of 217 patients, followed-up periodically, with an average observation time of 83.4 months and an interval of between 5 and 155 months. We also studied the frequency of remission and the influence of a group of variables on this, as well as the mortality and its causes. Results. The clinical state of the patients was: remission 77 (35.4%); pharmacological remission 45 (20.7%); significant improvement 70 (32.2%); the same or worse 5 (2.3%); deaths 11 (5%), and unknown 9 (4.1%). The cases with thymomas had a more unsatisfactory course than the other patients, with fewer remissions and greater mortality. Over the first five years of the evolution of the disease, there was a 30% rate of remission; after five years this rose to 35-40% and after ten years reached 47%. The age of the patient, duration of symptoms, histology of the thymus, age of onset of the disease and duration of follow-up did not have any significant effect (p< 0.05) on the long-term evolution of the thymectomy, in contrast to the gravity of the condition according to Osserman’s scale. Conclusion. The results of thymectomy, in our study were good and similar to the results reported in the international literature (AU)

Introducción. La timectomía es un procedimiento quirúrgico ampliamente aceptado en el tratamiento de la miastenia gravis. Objetivo. Describir la evolución a largo plazo de 217 pacientes miasténicos a quienes se efectuó timectomía en el Hospital Clínico Quirúrgico Hermanos Ameijeiras de La Habana, Cuba. Pacientes y métodos. Se determinó el estado evolutivo de 217 pacientes, seguidos periódicamente, con un tiempo de observación promedio de 83,4 meses y un intervalo de entre 15 y 155 meses. Asimismo, se estudió la frecuencia de remisión y la influencia de un grupo de variables sobre ella, así como la mortalidad y sus causas. Resultados. El estado clínico de los pacientes fue: remisión 77 (35,4%); remisión farmacológica 45 (20,7%); mejoría significativa 70 (32,2%); igual o peor 5 (2,3%); fallecidos 11 (5%), y desconocido 9 (4,1%). Los casos con timoma evolucionaron menos favorablemente que el resto de los pacientes, pues pudo observarse una menor frecuencia de remisiones y una mayor mortalidad. En los primeros cinco años de evolución la frecuencia de remisiones fue del 30%; después de los cinco años aumentó hasta un 35-40%, y después de diez años alcanzó un 47%. La edad del paciente, la duración de los síntomas, la histología del timo, la edad de debut de la enfermedad y el tiempo de seguimiento no tuvieron una influencia significativa (p< 0,05) sobre la evolución a largo plazo de la timectomía, a diferencia de la gravedad de la enfermedad de acuerdo con la escala de Osserman. Conclusión. Los resultados de la timectomía en nuestro estudio fueron favorables y similares a los publicados internacionalmente (AU)

Suppression of experimental myasthenia gravis by monoclonal antibodies against MHC peptide region involved in presentation of a pathogenic T-cell epitope.

We have prepared monoclonal antibodies (mAbs) against an antigen-binding region of I-A, region 62-76 of I-Abeta(b), which is involved in the T-cell participation in the pathogenesis of EAMG. The mAbs reacted with its parent molecules and inhibited the proliferation of disease-related T-cells. Passive transfer of these mAbs suppressed the occurrence of clinical EAMG, which was accompanied by decreased T-cell and Ab responses to tAChR. The results indicated that blocking the function of disease-related MHC by targeting a disease-associated region on MHC molecules could be an effective, straightforward and feasible strategy for immunointervention in MG.

A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help.

Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by T cell-dependent autoantibodies that react with the nicotinic acetylcholine receptor (AChR) on muscle and interfere with neuromuscular transmission. Thus, selective inactivation of CD4(+) AChR-specific T helper cells should lower AChR Ab levels and ameliorate disease. In the Lewis rat model of EAMG, alpha chain residues 100-116 of the AChR represent the dominant T cell epitope, which is important in helping Ab responses to this autoantigen. In the present report, we have applied a new design technique that requires no knowledge of Ag receptor sequences on errant T cells in order to develop a synthetic peptide vaccine against T cells reactive with the aforementioned T cell epitope. Immunization with the peptide 1) induced polyclonal and monoclonal Ab, which inhibited AChR 100-116 stimulation of AChR-sensitized lymphocytes and recognized Vbeta15 containing T cell receptors on AChR 100-116-specific T cell lines and clones; 2) lowered AChR Ab levels; 3) reduced the loss of muscle AChR; and 4) lessened the incidence and severity of EAMG. These findings suggest a new strategy for the functional abrogation of epitope-specific T cells that could have potential application to human autoimmune diseases.

Prevention of passively transferred experimental autoimmune myasthenia gravis by a phage library-derived cyclic peptide.

Many pathogenic antibodies in myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are directed against the main immunogenic region (MIR) of the acetylcholine receptor (AcChoR). These antibodies are highly conformation dependent; hence, linear peptides derived from native receptor sequences are poor candidates for their immunoneutralization. We employed a phage-epitope library to identify peptide-mimotopes capable of preventing the pathogenicity of the anti-MIR mAb 198. We identified a 15-mer peptide (PMTLPENYFSERPYH) that binds specifically to mAb 198 and inhibits its binding to AcChoR. A 10-fold increase in the affinity of this peptide was achieved by incorporating flanking amino acid residues from the coat protein as present in the original phage library. This extended peptide (AEPMTLPENYFSERPYHPPPP) was constrained by the addition of cysteine residues on both ends of the peptide, thus generating a cyclic peptide that inhibited the binding of mAb 198 to AcChoR with a potency that is three orders of magnitude higher when compared with the parent library peptide. This cyclic peptide inhibited the in vitro binding of mAb 198 to AcChoR and prevented the antigenic modulation of AcChoR caused by mAb 198 in human muscle cell cultures. The cyclic peptide also reacted with several other anti-MIR mAbs and the sera of EAMG rats. In addition, this peptide blocked the ability of mAb 198 to passively transfer EAMG in rats. Further derivatization of the cyclic peptide may aid in the design of suitable synthetic mimotopes for modulation of MG.