DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0024
6 Molecular and Cell Biology of Autoantibodies and Autoimmunity
by an active transport system involving the nuclear pores and specific signal se-
quences. Pore specific proteins have been identified. The composition of the
nuclear lamina, a proteineous network located between the inner nuclear mem-
brane and chromatin, is now well understood. The three lamins of the nuclear
lamina have been cloned, and sequence analysis has revealed that they are related
to intermediate filaments. This relationship supports their roles as possible nu-
cleoskeletal components. In view of their diagnostic interest, antinuclear autoan-
tibodies (ANA) are the subject of intensive research. Autoantibodies directed
against DNA, DNA binding proteins, ribonucleoproteins, enzymes and factors
involved in nucleic acid metabolism have been characterized. Some of these an-
tigens have been sequenced and their function(s) unambiguously demonstrated.
In contrast, antibodies directed against the nuclear envelope have not been exten-
sively examined, with the exception of those directed against lamins. We have been
interested in this category of autoantibodies which represent a low percentage of
total ANA (2-3%). 21 sera which recognize proteins of the nuclear envelope have
been studied by immunofluorescence, immunoblotting and immunoprecipitation.
They have allowed us to isolate two sets of antigens: the lamins and a 200 kilo-
dalton protein.
1) The lamins:
11 sera were shown to contain antibodies to lamins [1,2]. Sera from 8 patients
contained autoantibodies reacting with lamin B, whereas sera from the other 3 pa-
tients reacted with lamins A and C. All patients (9 women and 2 men) had a
chronic autoimmune disorder which does not fulfill the usual criteria for a diag-
nosis of systemic lupus erythematosus. Instead, the disorder was characterized by
acute or chronic hepatitis, steroid-responsive blood cytopenia and cutaneous
angiitis or probable brain vasculitis. Eight patients had at least two of these condi-
tions. A peculiar feature of these antibodies is their high affinity and broad
species specificity. Moreover, two anti-lamin B sera were found to be directed
against epitopes which were also found in non lamin proteins, which may have
intermediate filaments anchoring properties [3, 4].
2) A 200 kDa protein:
10 sera were shown to contain antibodies to a protein of 200 kDa [5]. This pro-
tein has now been identified as the major glycoprotein of the nuclear pore com-
plex [6]. Strikingly, all of the patients suffered from primary biliary cirrhosis
(PBC). As control serum displayed no reactivity, anti-200 kDa polypeptide an-
tibodies can be considered as a new marker of this disease. To evaluate the in-
cidence of such antibodies, 150 sera from patients with PBC were screened for
the presence of nuclear envelope antibodies. 40 sera (27%) were shown to contain
antibodies to the 200 kDa protein. We are currently searching for a peculiar
clinical and histological feature which may characterize the subset of patients hav-
by an active transport system involving the nuclear pores and specific signal se-
quences. Pore specific proteins have been identified. The composition of the
nuclear lamina, a proteineous network located between the inner nuclear mem-
brane and chromatin, is now well understood. The three lamins of the nuclear
lamina have been cloned, and sequence analysis has revealed that they are related
to intermediate filaments. This relationship supports their roles as possible nu-
cleoskeletal components. In view of their diagnostic interest, antinuclear autoan-
tibodies (ANA) are the subject of intensive research. Autoantibodies directed
against DNA, DNA binding proteins, ribonucleoproteins, enzymes and factors
involved in nucleic acid metabolism have been characterized. Some of these an-
tigens have been sequenced and their function(s) unambiguously demonstrated.
In contrast, antibodies directed against the nuclear envelope have not been exten-
sively examined, with the exception of those directed against lamins. We have been
interested in this category of autoantibodies which represent a low percentage of
total ANA (2-3%). 21 sera which recognize proteins of the nuclear envelope have
been studied by immunofluorescence, immunoblotting and immunoprecipitation.
They have allowed us to isolate two sets of antigens: the lamins and a 200 kilo-
dalton protein.
1) The lamins:
11 sera were shown to contain antibodies to lamins [1,2]. Sera from 8 patients
contained autoantibodies reacting with lamin B, whereas sera from the other 3 pa-
tients reacted with lamins A and C. All patients (9 women and 2 men) had a
chronic autoimmune disorder which does not fulfill the usual criteria for a diag-
nosis of systemic lupus erythematosus. Instead, the disorder was characterized by
acute or chronic hepatitis, steroid-responsive blood cytopenia and cutaneous
angiitis or probable brain vasculitis. Eight patients had at least two of these condi-
tions. A peculiar feature of these antibodies is their high affinity and broad
species specificity. Moreover, two anti-lamin B sera were found to be directed
against epitopes which were also found in non lamin proteins, which may have
intermediate filaments anchoring properties [3, 4].
2) A 200 kDa protein:
10 sera were shown to contain antibodies to a protein of 200 kDa [5]. This pro-
tein has now been identified as the major glycoprotein of the nuclear pore com-
plex [6]. Strikingly, all of the patients suffered from primary biliary cirrhosis
(PBC). As control serum displayed no reactivity, anti-200 kDa polypeptide an-
tibodies can be considered as a new marker of this disease. To evaluate the in-
cidence of such antibodies, 150 sera from patients with PBC were screened for
the presence of nuclear envelope antibodies. 40 sera (27%) were shown to contain
antibodies to the 200 kDa protein. We are currently searching for a peculiar
clinical and histological feature which may characterize the subset of patients hav-