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T S Lieu

Publications and source records attributed to T S Lieu.

11 recordsLinked to original sources
PubMed1992

Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.

We have cloned and sequenced a 46-kD Ro/SS-A autoantigen gene that is the human homologue of the calcium-binding protein, calreticulin. The sequence of this 46-kD Ro/SS-A protein (calreticulin) has significant homology to lambda Ral-1, a recombinant cDNA clone corresponding to a major antigen of the nematode, Onchocerca volvulus, the infectious agent of onchocerciasis. We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin). 20 of 22 sera from Liberian onchocerciasis patients who had no known evidence of autoimmune disease were found to contain antibodies that reacted with the 46-kD Ro/SS-A (calreticulin) by immunoblot analysis. Characteristic of sera reactive with Ro/SS-A antigens, some onchocerciasis sera also immunoprecipitated the Ro/SS-A-associated hY RNAs. In addition, a monoclonal antibody raised against O. volvulus organisms reacted to purified human WiL-2 cell 46 kD Ro/SS-A antigen (calreticulin) by ELISA. These results strongly suggest that onchocerciasis patients produce antibodies that crossreact with the 46-kD human Ro/SS-A autoantigen (calreticulin) and raise the possibility that infectious organisms such as O. volvulus might play a triggering or exacerbating role in the human Ro/SS-A autoimmune response.

Amino Acid Sequence↗
PubMed1991

Correlation between dermal interstitial immunoglobulin G and hypergammaglobulinemia.

The diffuse dermal immunofluorescence (DDIF) observed in human skin biopsies that is produced by fluorochrome-conjugated antisera reactive with human immunoglobulin G (IgG) has commonly been viewed in the past as an artifact of direct immunofluorescence microscopy. However, it has been our belief that DDIF, which has been observed in 14% of the biopsies processed in our laboratory, might represent an in vivo phenomenon of excess unbound dermal interstitial immunoglobulin G reflective of elevated serum IgG levels. To examine this hypothesis, we carried out a blinded prospective study of the frequency of DDIF in two groups of age- and sex-matched patients that differed with respect to the presence or absence of serum hypergammaglobulinemia (gamma globulin greater than 2.5 mg/100 ml). The subjective intensity of DDIF and the fluorescein-isothiocyanate (FITC) conjugated anti-human IgG antibody titer at which point DDIF disappeared were both compared with serum gamma globulin levels. Also, the amount of IgG that could be extracted from biopsy specimens by an overnight phosphate-buffered saline (PBS) elution procedure was quantified by solid-phase immunoassay. We noted a trend of increased DDIF intensity with increasing serum gamma globulin levels. In addition, there was a relatively weak but significant positive correlation between DDIF endpoint titers and serum gamma globulin levels (p = 0.05, r = 0.429). The strongest positive statistical correlation observed in the study was between the quantities of IgG that could be eluted from skin biopsies and serum gamma globulin levels (p = 0.01, r = 0.599). These findings suggest that DDIF is a true biologic phenomenon reflective of elevated serum gamma globulin levels and demonstrate that simple overnight elution of unbound dermal IgG can unmask the presence of disease-related, specifically-bound IgG.

Adult↗
PubMed1991

Molecular characterization of the Ro/SS-A autoimmune response.

Human Ro/SS-A (Ro) antibodies (anti-Ro) are frequently seen in the circulation of patients with several subsets of photosensitive cutaneous lupus erythematosus (LE) and related disorders. Experimental observations have suggested that anti-Ro reacting with Ro antigens that are expressed abberantly within the epidermis might play a causal role in LE-specific skin disorders such as subacute cutaneous LE (SCLE) and neonatal LE. In this article, we will review the progress that has recently been achieved toward gaining a better understanding of the molecular configuration, genetic regulation, and function of the Ro ribonucleoprotein (RNP) antigenic complex as well as the autoimmune response with which it is associated. Work in this area has recently revealed the existence of multiple Ro autoantigen-bearing polypeptides including a 46-kd Ro protein that is virtually identical to calreticulin, a highly conserved, calcium-binding protein that is normally associated with the endoplasmic reticulum. The implications of these observations with respect to the pathogenesis of anti-Ro-associated LE skin lesions are explored.

Antibodies, Antinuclear↗
PubMed1990

Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus.

In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well-documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus.

Adult↗
PubMed1990

IgG subclasses in the serum and skin in subacute cutaneous lupus erythematosus and neonatal lupus erythematosus.

IgG subclasses differ in their biologic and chemical properties, such as complement fixation, protein and cellular binding, and placental transfer. In this study, IgG subclasses of anti-Ro/SSA antibodies in subacute cutaneous lupus (SCLE) and neonatal lupus (NLE) are examined in the serum and in the skin. IgG subclasses in NLE beginning in utero (NLE-heart disease) are compared to subclasses in NLE beginning after birth (NLE-skin disease). Human skin was grafted onto athymic mice, mice were injected with one of eight anti-Ro/SSA maternal NLE sera (four heart block, four skin disease) or seven anti-Ro/SSA SCLE sera, and grafts were examined for IgG subclasses using monoclonal anti-human IgG subclass reagents in an immunofluorescent technique. Lesional skin was examined from four SCLE patients. IgG1 was the only IgG subclass detected in the grafts and skin lesions. IgG1 was the predominant anti-Ro/SSA IgG subclass detected in SCLE and NLE sera in an ELISA using a synthetic Ro/SSA polypeptide. These studies show that the maternal anti-Ro/SSA autoantibodies in NLE-heart disease sera are predominantly IgG1 and are therefore likely to be present in the fetus at the time of gestation, when heart block usually develops. Second, differences in the clinical presentations of NLE (in utero vs. postnatal disease) cannot be attributed to differences in anti-Ro/SSA IgG subclasses. Finally, the subclass bound in the skin in SCLE is IgG1, a subclass capable of mediating tissue injury via complement or cellular effectors.

Animals↗
PubMed1990

Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen.

Ro/SS-A antibodies are found in a number of human autoimmune disorders including Sjogren's syndrome and several systemic lupus erythematosus-related disorders. These heterogeneous autoantibodies are known to recognize several distinct cellular antigens. With synthetic oligonucleotides corresponding to amino acid sequence information we have isolated a full-length cDNA clone which encodes a human Ro ribonucleoprotein autoantigen. The 1,890-base pair clone contains an open reading frame that encodes a 417-amino acid, 48-kD polypeptide that migrates aberrantly at 60 kD by SDS-PAGE. Rabbit antibodies raised against this protein's recently described amino-terminal epitope react with a previously identified 52-kD human Ro protein and immunoprecipitate the human cytoplasmic RNAs. Ultraviolet light cross-linking studies suggest that this Ro protein binds each of the four major human cytoplasmic RNAs. The deduced amino acid sequence is 63% homologous to an Onchocerca volvulus antigen. Southern filter hybridization analysis indicates that this gene is not highly polymorphic and exists as a single copy in the human genome. Chromosomal localization studies place this gene on the short arm of chromosome 19 near the gene encoding the low density lipoprotein receptor.

Amino Acid Sequence↗
PubMed1990

A human Ro/SS-A autoantigen is the homologue of calreticulin and is highly homologous with onchocercal RAL-1 antigen and an aplysia "memory molecule".

The Ro/SS-A (Ro) autoantigens consist of at least four immunologically distinct proteins which are recognized by autoantibodies typically found in sera from patients with primary Sjogren's syndrome and in subsets of patients with lupus erythematosus. We recently isolated a 1.9-kb human cDNA clone which encodes one of these Ro autoantigens. Synthetic oligonucleotides corresponding to the human Ro sequence were used to amplify the homologous gene from a murine B cell cDNA library using the polymerase chain reaction. The mouse cDNA-encoded amino acid sequence was found to be 94% homologous to the human Ro sequence and is 100% homologous to murine calreticulin, a high affinity calcium-binding protein which resides in the endoplasmic and sarcoplasmic reticulum. The amino acid sequence of rabbit calreticulin is 92% homologous to both murine calreticulin and human Ro. Onchocerca volvulus and Drosophila melanogaster also have molecules that are highly homologous to human Ro. In addition, human Ro has a molecular mass, isoelectric point, and significant amino acid sequence similar to the Aplysia californica snail neuronal protein 407. These homologies suggest that this Ro protein has a very basic cellular function(s) which may in part involve calcium binding.

Amino Acid Sequence↗
PubMed1989

A major autoepitope is present on the amino terminus of a human SS-A/Ro polypeptide.

A human SS-A/Ro antigen is present on the polypeptide component of a particle composed of hyRNA and a 60 kD protein. We have now purified the Wil-2 cell 60 kilo dalton (kD) SS-A/Ro protein and determined its amino-terminal amino acid sequence. A synthetic peptide corresponding to residues 7 to 24 of this sequence (RoSP7-24) exhibited enzyme-linked immunosorbent assay (ELISA) binding activity with immunodiffusion-defined, monospecific anti-SS-A/Ro sera. In addition, ELISA binding of monospecific anti-SS-A/Ro sera to native SS-A/Ro antigen was partially inhibited (35%) by KLH-RoSP7-24. Sera from patients known to frequently produce precipitating anti-SS-A/Ro antibody (subacute cutaneous lupus erythematosus [SCLE], 56 patients; Sjögren's syndrome [SS], 41 patients; mothers of infants with neonatal LE [NLE], 10 individuals; infants with congenital heart block [CHB], 5 patients) were tested for reactivity to RoSP7-24 in ELISA. Overall, 38% of SCLE sera, 36% of SS sera, 50% of maternal NLE sera and 20% of CHB infant sera had anti-RoSP7-24 binding levels greater than 2 standard deviations above the mean of that of normal individuals. Of the sera which had anti-SS-A/Ro detected by double immunodiffusion and/or counterimmunoelectrophoresis, 68% of SCLE patients, 71% of SS patients, 55% of NLE mothers and 20% of CHB infants had significantly elevated RoSP7-24 ELISA binding levels. These findings strongly suggest that a major autoepitope of native human SS-A/Ro resides on the amino terminal portion of the Wil-2 SS-A/Ro 60 kD polypeptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗
PubMed1989

Ro/SS-A and the pathogenic significance of its antibodies.

Ro/SS-A is a soluble cellular protein to which antibodies are frequently directed in patients with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE)-related disorders. The pathogenic significance of these antibodies is uncertain. Our effort to further characterize the immunological and structural nature of Ro/SS-A suggests that the native human Ro/SS-A molecule is not glycosylated and consists of two disulfide linked domains. The amino terminus of the smaller domain contains a major epitope reactive with anti-Ro/SS-A sera. We have isolated and characterized a complementary DNA (cDNA) clone which encodes the Ro/SS-A polypeptide. The Ro/SS-A gene does not appear to be highly polymorphic and exists as a single copy on the short arm of chromosome 19. The isolation of the Ro/SS-A cDNA should allow for a more complete characterization of Ro/SS-A epitopes which should help further elucidate the importance of Ro/SS-A antibodies in the pathogenesis of disease.

Antibodies, Antinuclear↗
PubMed1987

Relationship between circulating anti-Ro/SS-A antibody levels and skin disease activity in subacute cutaneous lupus erythematosus.

Anti-Ro/SS-A antibody levels in 80 serum specimens from 12 patients with subacute cutaneous lupus erythematosus (SCLE) were determined by immunodiffusion and enzyme-linked immunosorbent assay in order to examine the changes in this autoantibody response with time and to study the relationship between levels of this antibody and SCLE skin disease activity. Anti-Ro/SS-A antibody levels were found to vary considerably over time in a given patient when measured by both assays. Several patients who did not have detectable levels of this antibody at the time of their initial examination were found to be antibody positive at follow-up examinations. However, no significant relationship was found between antibody levels in either assay and SCLE skin disease activity. While not ruling out a pathogenetic role for this antibody in the elicitation of SCLE skin lesions, these results would suggest that other factors are likely to be involved.

Adult↗