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

Hi, Dan. Glad to see that you're doing some research!

What they aren't saying in this article is the recent "revelation" that vitamin D "might be" crucial in the prevention of development of autoimmune diseases. It's long been known that us Northern Europeans tend to have more AIs.

Studies such as this one don't take into account that people move around the planet and it's more difficult to say if it is actual genetics and/or environment that affects the development of AIs.

I'm surprised they even attempt to classify MuSK patients, since they have only been recently identified and I doubt the number of subjects for any study is that large.

I personally would be more interested in what studies they are doing in an attempt to cure this awful disease, and other AIs!

Annie