PMID- 10050892
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190513
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 122 ( Pt 1)
DP  - 1999 Jan
TI  - Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of
      patients with paraneoplastic neurological disorders.
PG  - 27-39
AB  - The identification of antineuronal antibodies has facilitated the diagnosis of
      paraneoplastic neurological disorders and the early detection of the associated
      tumours. It has also led to the cloning of possibly important neuron-specific
      proteins. In this study we wanted to identify novel antineuronal antibodies in
      the sera of patients with paraneoplastic neurological disorders and to clone the 
      corresponding antigens. Serological studies of 1705 sera from patients with
      suspected paraneoplastic neurological disorders resulted in the identification of
      four patients with antibodies that reacted with 37 and 40 kDa neuronal proteins
      (anti-Ma antibodies). Three patients had brainstem and cerebellar dysfunction,
      and one had dysphagia and motor weakness. Autopsy of two patients showed loss of 
      Purkinje cells, Bergmann gliosis and deep cerebellar white matter inflammatory
      infiltrates. Extensive neuronal degeneration, gliosis and infiltrates mainly
      composed of CD8+ T cells were also found in the brainstem of one patient. In
      normal human and rat tissues, the anti-Ma antibodies reacted exclusively with
      neurons and with testicular germ cells; the reaction was mainly with subnuclear
      elements (including the nucleoli) and to a lesser degree the cytoplasm. Anti-Ma
      antibodies also reacted with the cancers (breast, colon and parotid) available
      from three anti-Ma patients, but not with 66 other tumours of varying
      histological types. Preincubation of tissues with any of the anti-Ma sera
      abrogated the reactivity of the other anti-Ma immunoglobulins. Probing of a human
      complementary DNA library with anti-Ma serum resulted in the cloning of a gene
      that encodes a novel 37 kDa protein (Mal). Recombinant Mal was specifically
      recognized by the four anti-Ma sera but not by 337 control sera, including those 
      from 52 normal individuals, 179 cancer patients without paraneoplastic
      neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients 
      with non-cancer-related neurological disorders. The expression of Mal mRNA is
      highly restricted to the brain and testis. Subsequent analysis suggested that Mal
      is likely to be a phosphoprotein. Our study demonstrates that some patients with 
      paraneoplastic neurological disorders develop antibodies against Mal, a new
      member of an expanding family of 'brain/testis' proteins.
FAU - Dalmau, J
AU  - Dalmau J
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
      10021, USA.
FAU - Gultekin, S H
AU  - Gultekin SH
FAU - Voltz, R
AU  - Voltz R
FAU - Hoard, R
AU  - Hoard R
FAU - DesChamps, T
AU  - DesChamps T
FAU - Balmaceda, C
AU  - Balmaceda C
FAU - Batchelor, T
AU  - Batchelor T
FAU - Gerstner, E
AU  - Gerstner E
FAU - Eichen, J
AU  - Eichen J
FAU - Frennier, J
AU  - Frennier J
FAU - Posner, J B
AU  - Posner JB
FAU - Rosenfeld, M R
AU  - Rosenfeld MR
LA  - eng
SI  - GENBANK/AF037364
GR  - NS-26064/NS/NINDS NIH HHS/United States
GR  - NS01625-04/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Antigens)
RN  - 0 (Epitopes)
RN  - 0 (Immune Sera)
RN  - 0 (Ma1 antigen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
CIN - Brain. 1999 Jan;122 ( Pt 1):3-4. PMID: 10050889
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Antigens/genetics/*immunology/metabolism
MH  - Base Sequence/genetics
MH  - Brain/metabolism
MH  - Brain Diseases/*immunology/pathology/physiopathology
MH  - Cloning, Molecular
MH  - Epitopes/physiology
MH  - Female
MH  - Humans
MH  - Immune Sera/analysis/*immunology
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Neoplasms/immunology
MH  - Paraneoplastic Syndromes/*immunology/pathology/physiopathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins/immunology
MH  - Testis/metabolism
EDAT- 1999/03/02 00:00
MHDA- 1999/03/02 00:01
CRDT- 1999/03/02 00:00
PHST- 1999/03/02 00:00 [pubmed]
PHST- 1999/03/02 00:01 [medline]
PHST- 1999/03/02 00:00 [entrez]
AID - 10.1093/brain/122.1.27 [doi]
PST - ppublish
SO  - Brain. 1999 Jan;122 ( Pt 1):27-39. doi: 10.1093/brain/122.1.27.