DOI Page / Citation link:
https://doi.org/10.11588/diglit.48120#0049
Abstracts
31
Ul-68Kd Protein-Positive Mixed Connective Tissue Disease is
Associated with HLA-DR4 and Appears Genetically Distinct from
Systemic Lupus Erythematosus
R.W. Hoffman, L. J. Rettenmaier, Y. Takeda, and G. C. Sharp
University of Missouri-Columbia and the Harry S. Truman Veterans Hospital Columbia,
MO 65201, USA
Mixed connective tissue disease (MCTD) and systemic lupus erythematosus
(SLE) are two prototype multi-systemic autoimmune diseases of unknown
etiology. These two diseases are characterized by distinct clinical features and the
presence of distinct patterns of autoantibodies which are reactive with selfan-
tigens, including autoantibodies reactive with small nuclear ribonucleoproteins
(snRNPs). The existence of MCTD as a distinct disease entity is, however, con-
troversial. Some investigators consider MCTD to be a subset of SLE while others
include it within the spectrum of scleroderma.
To investigate whether MCTD is a distinct entity we studied 20 North
American Caucasian MCTD patients whose sera were reactive with the Ul-68Kd
protein antigen of the snRNP complex by an enzyme-linked immunoabsorbent
assay (ELISA), using the purified 68Kd protein antigen or a recombinant fusion
protein for the antigen. Sera from all 20 MCTD patients studied were positive for
reactivity with the 68Kd protein antigen; 12 of 38 SLE patients sera were positive
for reactivity with the B/B' and D proteins (the Sm antigen) of the snRNP com-
plex. We compared the MCTD patients to 38 SLE patients and normal controls.
All patients classified as MCTD had typical overlapping clinical features and
met the classification criteria of Porter, et al. (Arthritis Rheum. 1989: 31, 219);
all patients classified as SLE met 4 or more of the revised American Rheumatism
Association criteria for SLE. All patients were all examined using the snRNP
ELISA assay to determine whether their sera reacted with the 68Kd, A, B/B, or
D proteins or the snRNP complex. HLA-A, B, C typings were performed using
standard the NIH complement-dependent cytotoxicity technique. HLA-DR and
HLA-DQ typing were performed using a two-color fluorescence technique.
Results are shown below. HLA-DR4 was increased in MCTD (60%) versus
(30%) controls (P<0.02) and versus (18%) SLE (P<0.002). The supratypic HLA
marker HLA-DRw53 was increased in (80%) MCTD patients versus (53%) con-
trols (P<0.008) and versus (37%) SLE (P<0.004). The supratypic HLA marker
HLA-DRw52 was increased in SLE (76%) versus (30%) MCTD (P<0.004). HLA-
DR3 was increased in SLE (47%) versus (21%) controls P <0.004. HLA-DR2 was
increased in MCTD (50%) and SLE (53%) versus controls (27%) P<0.002.
31
Ul-68Kd Protein-Positive Mixed Connective Tissue Disease is
Associated with HLA-DR4 and Appears Genetically Distinct from
Systemic Lupus Erythematosus
R.W. Hoffman, L. J. Rettenmaier, Y. Takeda, and G. C. Sharp
University of Missouri-Columbia and the Harry S. Truman Veterans Hospital Columbia,
MO 65201, USA
Mixed connective tissue disease (MCTD) and systemic lupus erythematosus
(SLE) are two prototype multi-systemic autoimmune diseases of unknown
etiology. These two diseases are characterized by distinct clinical features and the
presence of distinct patterns of autoantibodies which are reactive with selfan-
tigens, including autoantibodies reactive with small nuclear ribonucleoproteins
(snRNPs). The existence of MCTD as a distinct disease entity is, however, con-
troversial. Some investigators consider MCTD to be a subset of SLE while others
include it within the spectrum of scleroderma.
To investigate whether MCTD is a distinct entity we studied 20 North
American Caucasian MCTD patients whose sera were reactive with the Ul-68Kd
protein antigen of the snRNP complex by an enzyme-linked immunoabsorbent
assay (ELISA), using the purified 68Kd protein antigen or a recombinant fusion
protein for the antigen. Sera from all 20 MCTD patients studied were positive for
reactivity with the 68Kd protein antigen; 12 of 38 SLE patients sera were positive
for reactivity with the B/B' and D proteins (the Sm antigen) of the snRNP com-
plex. We compared the MCTD patients to 38 SLE patients and normal controls.
All patients classified as MCTD had typical overlapping clinical features and
met the classification criteria of Porter, et al. (Arthritis Rheum. 1989: 31, 219);
all patients classified as SLE met 4 or more of the revised American Rheumatism
Association criteria for SLE. All patients were all examined using the snRNP
ELISA assay to determine whether their sera reacted with the 68Kd, A, B/B, or
D proteins or the snRNP complex. HLA-A, B, C typings were performed using
standard the NIH complement-dependent cytotoxicity technique. HLA-DR and
HLA-DQ typing were performed using a two-color fluorescence technique.
Results are shown below. HLA-DR4 was increased in MCTD (60%) versus
(30%) controls (P<0.02) and versus (18%) SLE (P<0.002). The supratypic HLA
marker HLA-DRw53 was increased in (80%) MCTD patients versus (53%) con-
trols (P<0.008) and versus (37%) SLE (P<0.004). The supratypic HLA marker
HLA-DRw52 was increased in SLE (76%) versus (30%) MCTD (P<0.004). HLA-
DR3 was increased in SLE (47%) versus (21%) controls P <0.004. HLA-DR2 was
increased in MCTD (50%) and SLE (53%) versus controls (27%) P<0.002.