[imdan]

1. Introduction
Myasthenia gravis with antibodies to the muscle specific receptor
tyrosine kinase (MuSK-MG) is a rare disease that covers 5–8% of all
MG cases. Its history is a good example of fruitful interaction between
clinical observation and experimental evidence; such co-operation
has steadily enhanced our knowledge of disease mechanisms and
has been improving its management.
The pathogenic scenario of MuSK-MG is remarkably different from
that of “typical” MG associated with antibodies to the acetylcholine
receptor (AChR-MG). Thymus histological alterations, such as follicular
hyperplasia and thymoma, are commonly found in AChR-MG, where
they are thought to play a crucial role in the disease initiation. In particular,
the hyperplastic thymus contains all the cellular elements and
the inflammatory microenvironment required for the generation of anti-AChR antibody response [1,2]; thymoma is thought to be

responsible for impaired selection of auto-reactive T cells and reduced
generation of T regulatory cells [3,4]. On the other hand,
thymus alterations are very rare in MuSK-MG, where thymus histology
is mostly normal-for-age, with sparse lymphoid infiltrates [5,6].
Antibodies to MuSK are prevalently IgG4 and, differently from anti-
AChR antibodies (mostly IgG1 and IgG3), are unable to activate
complement and relatively inefficient in inducing antigen modulation
[7,8]; as disease animal models suggest their effector mechanism
appears to involve direct inhibition of MuSK function [9].
In contrast to the relatively uniform frequency of AChR-MG [10],
the positive rate of anti-MuSK antibodies in patients with anti-AChR
negative MG varies remarkably in different countries, with the lowest
rate in Norway [11] and the highest in Italy and Turkey [12,13]. These
findings are in line with the observation that, in Europe and North
America, MuSK-MG frequency seems to be inversely correlated to
latitude, with the highest prevalence around 40° north of the Equator
[14]. Moreover, in U.S. centers, a significantly higher rate of MuSK Abs
was reported in African-Americans than in whites [15]. The disease
shows a striking prevalence in women, with more than 70% female
patients in all studies, and a mean age of onset younger than 40
years in most patient series [16]. Though few studies have investigated
genetic susceptibility, a strong association with HLA-DQ5 was
reported in two independent European surveys [17,18]. Thus, it
appears that, as in other autoimmune diseases, genetic and hormonal
factors play a relevant role in MuSK-MG etiology, with regional differences
in prevalence suggesting environmental exposures so far unknown
[19]. .....snip....
(Diagnosis and therapy of myasthenia gravis with antibodies to muscle-specific kinase
Amelia Evoli a,⁎, Luca Padua a,b
a Institute of Neurology, Catholic University, Largo F. Vito 1, 00168 Roma, Italy
b Fondazione Don Carlo Gnocchi Onlus, Piazzale Morandi 6, 20121 Milano, Italy
a r t i c l e i n f o a b s t r a c t
Article history:
Accepted 12 March 2013
Available online 25 March 2013)..journal homepage

Hmmmm interesting that latitude /environment may play a role.

Dan