The majority of antibodies to the acetylcholine receptor (AcChoR), both in the human disease myasthenia gravis and in its experimental models, are directed against an extracellular area of the AcChoR a subunit called the main immunogenic region (MIR). We have studied the binding of anti-AcChoR monoclonal antibodies (mAbs) to 26 synthetic peptides corresponding to the hydrophilic parts of the human AcChoR a subunit. The binding sites for eight anti-MIR mAbs and for eight anti-a-subunit, non-anti-MiIR mAbs were localized. Anti-MIR mAbs bound to one peptide corresponding to residues 63-80 of the human a subunit. A second panel of peptides corresponding to the various parts of the a-subunit segment 63-80 was synthesized. Anti-MIR antibodies bound to a peptide that contained the a-subunit sequence 67-76. Thus, a main constituent loop of the MIR is localized between residues 67 and 76 of the a subunit.
Antigenic modulation of acetylcholine receptor (AChR) is considered to contribute to the reduction of endplate AChR in myasthenia gravis (MG). Yet, the pathogenic significance of this mechanism is unclear. To investigate the in vivo role of AChR antigenic modulation we examined the ability of bivalent F(ab')2 and monovalent Fab fragments of monoclonal antibody (mAb) 35 to passively transfer experimental autoimmune MG (EAMG) in rats. mAb 35 which binds at the main immunogenic region (MIR) of the AChR causes severe EAMG without being involved in channel function. Compared to the intact mAb, F(ab')2 35 proved to be less potent but still capable of inducing moderate EAMG, whereas Fab 35 were totally ineffective. Furthermore, both intact and F(ab')2 35 induced mild EAMG in complement-depleted rats. These results (a) provide evidence that antigenic modulation of endplate AChR is sufficient to generate passive transfer of EAMG and (b) further support the pathogenic potential of the anti-MIR antibodies in MG.
Parasitic plants are widespread pathogens that infect numerous plant species and cause devastating agricultural losses. They efficiently withdraw water, nutrients and sugars from their hosts by fusing tissues and connecting their vasculature to the host vasculature. This ability to parasitize is found in a wide range of species and has evolved at least eleven independent times, suggesting a recurring and flexible developmental strategy. Despite multiple independent origins, a common feature to parasitism is the formation of an invasive organ termed the haustorium. Parasitic plants form haustoria in their stems or roots and use this structure to penetrate host tissues and form vascular connections, often with distantly related species. This ability to join to an unrelated species is remarkable, and together with the economic importance of parasitism, there is a strong need to further understand how parasitic plants infect their hosts. Here, we discuss the developmental basis for plant parasitism, focusing on haustorial initiation, penetration and vascular formation. We also discuss future directions and outstanding questions in this emerging field.
Objectives: The purposes of this study were to determine the epidemiological characteristics of muscle‐specific kinase‐myasthenia gravis (MuSK‐MG) in Greece and the IgG subclass of the anti‐MuSK antibodies.
Methods: This population‐based study was performed on MuSK‐MG patients in Greece between 1 January 1986 and 30 June 2006. Epidemiological and clinical data for 33 patients were collected. In addition, the distribution of anti‐MuSK IgG autoantibody subclasses in the sera of 14 patients was determined by immunoprecipitation.
Results: The average annual incidence was 0.32 patients/million population/year. On 1st July 2006, there were 33 prevalent cases, giving a point prevalence rate of 2.92/million (women 4.56 and men 1.25). In females, onset of MuSK‐MG occurred after the age of 30, whilst, in males, the disease appears in any decade. The female:male incidence ratio was 3.33:1, whilst the prevalence ratio was 3.65:1. Most patients presented with involvement of the facial and bulbar muscles. Amongst about 800 MG patients seropositive for antibodies against either the AChR or MuSK, one patient was found to be seropositive for anti‐MuSK antibodies and ambiguous for anti‐acetylcholine receptor (anti‐AChR) antibodies. The vast majority of anti‐MuSK antibodies were IgG4, whilst total IgG4 levels in these patients were similar to those in two healthy controls.
Conclusions: The incidence and prevalence of MuSK‐MG in Greece are amongst the highest reported previously for other countries. MuSK‐MG in Greece affects both sexes, but mainly females. The main epidemiological indices were calculated. The vast majority of anti‐MuSK antibodies were IgG4.
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