bromochloroacetic-acid and Lupus-Erythematosus--Systemic

Topics: Antibodies; Arthritis, Rheumatoid; Chronic Disease; Humans; Intermediate Filament Proteins; Keratins; Lupus Erythematosus, Systemic; Rheumatic Diseases; Scleroderma, Systemic; Sjogren's Syndrome; Spondylitis, Ankylosing; Vimentin

To get a better understanding of the abnormal differentiation or maturation of keratinocytes, we studied the expression and distribution of cytokeratin and involucrin in lesions from systemic lupus erythematosus patients. Two groups of 10 specimens each from systemic lupus erythematosus and normal controls were analyzed by two-dimensional gel electrophoresis, mass spectrometric protein identification, Western blotting and immunohistochemistry. Our results showed that keratin 1 (K1)/K10 together with the new synthesis of K6/K16 were down-regulated and that K5/K14, K2e and involucrin were up-regulated. We found that involucrin was strongly stained in lower epidermal cell layers while K1/10 was weakly stained, particularly when compared with staining in normal epidermis. Additionally, we found that the expression of involucrin was increased. These results imply an aberrant early and terminal differentiation stage in the epidermis of systemic lupus erythematosus, which may be associated with inflammatory cytokines released during the wound healing response of lesion.

Topics: Blotting, Western; Electrophoresis, Gel, Two-Dimensional; Humans; Immunohistochemistry; Keratins; Lupus Erythematosus, Systemic; Protein Precursors; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Lupus erythematosus (LE) is an autoimmune disease of unknown cause. Prevalence of oral involvement in patients with LE is uncertain but may vary from 9 to 45% in patients with systemic disease and from 3 to 20% in patients with chronic cutaneous involvement.. Incidence of oral lesions of LE and their clinical aspects were investigated. Their histopathologic features were analyzed, and the status of epithelial maturation was assessed through the expression patterns of cytokeratins.. Twenty-six patients (from 188 examined) presented oral lesions of LE. Most of them were females (19) with systemic disease (11). Clinical aspects of these lesions varied, and lips and buccal mucosa were most affected. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers only.. Oral lesions of LE show a variety of aspects, and their microscopic features are of a lichenoid mucositis with deep inflammatory infiltrate. Cytokeratins expression patterns are of hyperproliferative epithelium, and this phenomenon must be analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lichenoid Eruptions; Lupus Erythematosus, Systemic; Male; Middle Aged; Stomatitis

Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established.. To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis.. Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients.. Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis.. Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.

Topics: Antibodies; Arthritis, Rheumatoid; Biomarkers; Citrulline; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Immunoglobulin G; Intermediate Filament Proteins; Keratins; Lupus Erythematosus, Systemic; Reagent Kits, Diagnostic; Rheumatoid Factor; Sensitivity and Specificity; Sjogren's Syndrome

We analyzed the frequency and clinical correlates of antiperinuclear factor (APF) and antibodies to the stratum corneum of rat esophagus in 86 children with juvenile idiopathic arthritis (JIA), 32 children with juvenile systemic lupus erythematosus, and 52 healthy children. Forty-two patients with JIA (49%) were positive for APF. No association was observed between APF and current age, sex, JIA subtype, age at disease onset, or disease duration. APF was found in one patient with juvenile systemic lupus erythematosus and in no healthy child. Antibodies to the stratum corneum of rat esophagus were detected in 3 patients with polyarticular JIA. APF may be a valuable tool in the differential diagnosis of JIA.

Topics: Animals; Antibodies; Antibodies, Antinuclear; Arthritis, Juvenile; Child, Preschool; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Lupus Erythematosus, Systemic; Male; Rats; Reference Values; Rheumatoid Factor

Topics: Autoantibodies; Cell Nucleus; Cytoplasm; Humans; Keratinocytes; Keratins; Lupus Erythematosus, Systemic; Rheumatic Diseases; RNA Splicing

Antibodies to recombinant heterogeneous nuclear RNP core protein A1 were detected in sera from 27 of 58 patients with rheumatoid arthritis (RA) and from 7 of 31 patients with systemic lupus erythematosus, by immunoblotting and enzyme-linked immunosorbent assay. Protein A1 consists of 2 distinct domains: The N-terminal sequence is identical to a single-stranded DNA binding protein termed UP1, and the C-terminal domain shows a partial homology with keratin. All 7 A1-positive systemic lupus erythematosus sera reacted with UP1, whereas 9 of the 27 A1-positive RA sera did not. In RA, anti-A1 activity was significantly associated with antikeratin antibodies (AKA); these antibodies were present in 23 of 27 A1-positive sera and 10 of 31 A1-negative sera (P less than 0.01). Immunoabsorption with recombinant protein A1 resulted in a significant reduction of AKA titers in 6 of 10 RA sera tested, suggesting that AKA from RA patients may cross-react with the C-terminal portion of the heterogeneous nuclear RNP protein A1.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Immunoblotting; Keratins; Lupus Erythematosus, Systemic; Male; Middle Aged; Nuclear Proteins; Recombinant Proteins; snRNP Core Proteins; Viral Core Proteins

The role of transforming growth factor beta 2 (TGF-beta 2) in the pathogenesis of systemic sclerosis (SSc) was investigated by in situ hybridization of skin biopsies from six patients with SSc. Two patients with acute systemic lupus erythematosis (SLE), one with acute dermatomyositis (DM), and three healthy individuals were used as controls. TGF-beta 2 mRNA was found to be co-localized with pro alpha 1(I) collagen expression around dermal blood vessels in all patients with the inflammatory stage of SSc, whereas there was no expression of either gene in the dermis of patients in the fibrotic stage, the SLE patients or the normal controls. These findings provide evidence that TGF-beta 2 released by inflammatory cells around blood vessels may play a role in mediating the collagen gene disregulation in fibrosis.

Topics: Blood Vessels; Blotting, Northern; Dermatomyositis; Gene Expression; Humans; Keratins; Lupus Erythematosus, Systemic; Nucleic Acid Hybridization; Procollagen; RNA Probes; RNA, Messenger; Sclerosis; Skin Physiological Phenomena; Transforming Growth Factors

Skin biopsy specimens from 24 patients with different lichenoid skin diseases that had been proved histologically were studied immunohistologically. Marked differences were noted in the number of OKT6+/S100+ Langerhans cells within the epidermis and dermis in the lesional skin between lichen planus (and its related disease) and lupus erythematosus; in the former these cells were increased in number; in the latter they were decreased in number compared with those in uninvolved perilesional skin. Human lymphocyte antigen (HLA)-DR expression on keratinocytes was observed not only in lichenoid skin diseases but also in control cases without epidermal involvement. In the two cases of systemic lupus erythematosus, the uninvolved perilesional skin also show weak and focal HLA-DR reactivity in the basal layer. HLA-DR+ keratinocytes could play an important role at least in the perpetuation of epidermal cell damage mediated by T cells.

Topics: Epidermis; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Lichen Planus; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; T-Lymphocytes

A strong association between anti-SS-A/Ro and anti-SS-B/La antibodies and skin lesions has been well documented in subacute cutaneous lupus erythematosus and neonatal lupus erythematosis in which 70 to 80% of patients are female. In order to better understand the mechanisms of the influence of sex hormones on cutaneous lupus, we designed immunopathological in vitro experiments to evaluate the effects of estradiol and other sex steroids on the binding of SS-A/Ro- and SS-B/La-specific antibodies to cultured human keratinocytes from neonates. Cultured human keratinocytes incubated with antisera specific for SS-A/Ro or SS-B/La Ag were fixed with either acetone or paraformaldehyde and then analyzed in indirect immunofluorescent assays or by FACS analysis to detect cell surface IgG binding as an indirect measure of SS-A/Ro and SS-B/La Ag expression on the cell surface of keratinocytes. Estradiol (10(-5) to 10(-7) M) augmented binding of antiserum probes on the surface of cultured keratinocytes, with 10(-7) M estradiol showing the highest induction of cell surface binding of antisera specific for SS-A/Ro plus SS-B/La Ag (24.5% of cells were positive). In contrast, dihydrotestosterone, testosterone, and progesterone showed no augmentation. The augmentation by estradiol was partially inhibited by the antiestrogen nafoxidine. Estradiol augmented the relative incidence and absolute number of small or cuboidal cells binding antibodies specific for SS-A/Ro and SS-B/La Ag, whereas the number and incidence of larger differentiated cells binding anti-SS-A/Ro and anti-SS-B/La decreased significantly in cell cultures stimulated with estradiol. Flow cytometric analysis utilizing monospecific anti-SS-A/Ro or anti-SS-B/La sera showed that estradiol induced binding of anti-SS-A/Ro in 13.1% of cultured keratinocytes, of anti-SS-A/La in 14.4%, and of sera specific for both Ag in 21.4%. This direct association between estradiol and the augmentation of binding to the cell surface of human keratinocytes of IgG from antisera specific for SS-A/Ro and SS-B/La Ag may be a trigger factor of immunologic damage in lupus and may be important in the different sex rates observed in skin manifestation of subacute cutaneous and neonatal lupus erythematosis.

Topics: Adjuvants, Immunologic; Antibodies, Antinuclear; Antigens, Surface; Binding Sites, Antibody; Cell Differentiation; Cells, Cultured; Epidermal Cells; Epidermis; Estradiol; Humans; Infant, Newborn; Keratins; Lupus Erythematosus, Systemic

This paper reports three cases of lupus erythematosus (LE) associated with thymomas, all of which were discovered after the onset of LE. The diagnosis of LE was established by clinical and laboratory data. Histologically, the thymomas were of the three main types: epithelial, lympho-epithelial, and predominantly fusiform. In two cases, thymectomy did not modify the course of LE; in one vase, the absence of cytoplasmic secretory vesicles in the epithelial cells and the non-labelling of these cells by an antiserum thymic factor monoclonal antibody represented direct evidence of a functional thymus deficiency. Antikeratin antibodies were used to distinguish thymomas from lymphomas; epithelial thymomas exhibited the same keratin specificities as normal thymus, although the labelling pattern (net-like) was different. Labelling of epidermis with the same antiserum confirmed the theory of an epidermis-thymus relationship.

Topics: Aged; Animals; Antibodies, Monoclonal; Diagnosis, Differential; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lupus Erythematosus, Systemic; Lymphoma; Male; Mice; Middle Aged; Rabbits; T-Lymphocytes; Thymoma; Thyroid Neoplasms

In a previous study on lichen planus the morphology and significance of the colloid bodies were discussed (13). In the present study a description is given of 30 dermatoses with colloid bodies, observed among unselected patients. The colloid bodies develop as a result of damage to the epithelium caused by circulatory disorders with subsequent hypo- or anoxia. Lichenoid cell infiltration into the connective tissue--nearly always present--aggravates the process. Dyskeratosis, pyknosis and fibrinoid necrosis of the damaged cells occur and the nuclei disintegrate. The resultant colloid bodies may coalesce or scatter or be expelled from the epithelium according to the principles of apoptosis (6, 7). Besides circulatory disorders, purely local damage and pathological processes involving the tissues should be regarded as important factors. Although the colloid bodies are characteristic for various skin diseases, they do not have an absolutely clear diagnostic significance. In doubtful cases their presence may nevertheless be considered a valuable contribution and supplement to the diagnosis.

Topics: Amyloid; Darier Disease; Erythema Multiforme; Humans; Keratins; Lupus Erythematosus, Systemic; Skin Diseases; Skin Diseases, Vesiculobullous; Staining and Labeling

Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Cyclic AMP; Dermatitis; Fabry Disease; Humans; Keratins; Lupus Erythematosus, Systemic; Lysosomes; Psoriasis; Skin; Ultraviolet Rays; Vacuoles; Vitamin A Deficiency

Topics: Chloroquine; Epithelium; Fibroblasts; Histiocytes; Humans; Keratins; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Lymphocytes; Macrophages; Microscopy, Electron; Skin; Steroids; Viruses

Topics: Birth Injuries; Blister; Drug Eruptions; Epidermolysis Bullosa; Erythema; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Keratins; Listeria monocytogenes; Lupus Erythematosus, Systemic; Male; Maternal-Fetal Exchange; Miliaria; Nevus; Pregnancy; Pregnancy Complications; Rubella; Skin Diseases; Skin Diseases, Infectious; Stevens-Johnson Syndrome; Sucking Behavior; Syphilis, Congenital; Urticaria Pigmentosa