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1.
Br J Rheumatol ; 36(6): 700-2, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9236683

ABSTRACT

This case report describes transient neonatal Behçet's disease, with life-threatening complications in the neonate. Male Baby R developed blood-streaked diarrhoea 5 days after birth, followed by recurrent severe scarring orogenital ulceration and vasculitic skin lesions. In this sixth week of life, he developed stridor leading to a respiratory arrest and necessitating assisted ventilation. No infective cause was isolated. Baby R responded well to i.v. and subsequent oral steroid therapy. At 8 weeks old he had fully recovered and remains well. Baby R's mother was not previously known to have Behçet's disease. During the pregnancy, she began to suffer orogenital ulceration, associated with skin lesions typical of Behçet's disease. Mild orogenital ulceration has become recurrent.


Subject(s)
Behcet Syndrome/congenital , Behcet Syndrome/diagnosis , Pregnancy Complications/diagnosis , Adult , Autoantibodies/metabolism , Behcet Syndrome/immunology , Female , Humans , Immunoglobulin G/metabolism , Infant, Newborn , Male , Maternal-Fetal Exchange/immunology , Pregnancy , Pregnancy Complications/immunology , Time Factors
2.
Rheumatol Int ; 16(3): 89-94, 1996.
Article in English | MEDLINE | ID: mdl-8893372

ABSTRACT

Neither the incidence nor the severity of neonatal autoimmune disease correlates with maternal or neonatal autoantibody titres. However, there is now evidence that the agalactosyl [Gal(0)] fractions of autoantibodies are the most pathogenic. We found that systemic lupus erythematosus (SLE) mothers whose infants developed congenital heart block (CHB) had higher %Gal(0) at the end of pregnancy than did mothers of unaffected infants (P < 0.05) or control mothers (P < 0.01). Similarly, affected infants had higher %Gal(0) than control infants (P < 0.01). Then we studied the Gal(0) content of the anti-Ro and we found that it was higher in affected neonates than in unaffected neonates (P < 0.05), though there was no difference between the corresponding groups of mothers by this criterion. We propose that agalactosyl IgG may have a regulatory or effector role and that the risk of neonates developing maternal autoantibody-mediated disorders may be related to the quantity of agalacotsyl autoantibody present at birth, rather than to its absolute titre.


Subject(s)
Autoimmune Diseases/immunology , Immunoglobulin G/blood , Lupus Erythematosus, Systemic/immunology , Pregnancy Complications/immunology , RNA, Small Cytoplasmic , Adult , Autoantibodies/blood , Autoantigens/immunology , Female , Humans , Infant, Newborn , Maternal-Fetal Exchange , Pregnancy , Ribonucleoproteins/immunology , Tetanus Toxoid/immunology , SS-B Antigen
3.
Hum Reprod ; 10(10): 2564-9, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8567771

ABSTRACT

Immune reactions have effects at various concentrations in the reproductive process and autoantibodies may have an impact on fertility and the outcome of assisted conception. We measured the prevalence of and relation between antibodies to smooth muscle, nuclear, phospholipid and sperm antigens, and concentrations of immunoglobulins G, M and A and complement components C3 and C4, in the sera and follicular fluids of women with unexplained infertility (n = 30), endometriosis (n = 20), tubal infertility (n = 50) and the sera of 20 normal non-pregnant women. We assessed fertilization and successful pregnancy rates in relation to antibody status of infertile women after in vitro fertilization. All antibodies had a higher prevalence in infertile women compared with controls and this was significant for smooth muscle antibody in endometriosis (P < 0.05); anticardiolipin antibody in tubal infertility (P < 0.05); and antisperm antibody in all types of infertility (P < 0.001). There was no relation between presence of specific antibodies in serum or between serum and follicular fluids. Total biochemical pregnancy rate was higher with endometriosis (P = 0.05) but clinical pregnancy and live birth rates did not differ between groups or in relation to antibody status. Significant differences in immunoglobulin and complement components occurred in women with and without successful biochemical pregnancy.


Subject(s)
Autoantibodies/analysis , Fertilization in Vitro , Follicular Fluid/immunology , Infertility, Female/immunology , Pregnancy Outcome , Spermatozoa/immunology , Adult , Antibodies, Antinuclear/blood , Antibodies, Antiphospholipid/blood , Autoantibodies/blood , Autoantigens/immunology , Complement C3/metabolism , Complement C4/metabolism , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Infertility, Female/therapy , Male , Muscle, Smooth/immunology , Pregnancy
4.
Hum Reprod ; 9(7): 1253-6, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7962428

ABSTRACT

The expression of heat shock protein (hsp) 70 was investigated in endometrial samples from patients with unexplained infertility associated (n = 5) or not associated (n = 10) with endometriosis, and compared with a control group consisting of fertile women (n = 27) with reported menstrual disturbance. The expression of hsp, and in particular hsp 70, is up-regulated in response to many physico-biochemical insults as well as infection and possibly oncogenic transformation and is a good indicator of a biological system under stress. A significant over-expression of hsp 70 was found in the infertile groups (P < 0.001), suggesting that a stress response may be involved in the aetiology of unexplained infertility irrespective of the presence of endometriosis.


Subject(s)
Endometrium/metabolism , HSP70 Heat-Shock Proteins/metabolism , Infertility, Female/metabolism , Adult , Endometriosis/complications , Endometriosis/metabolism , Female , Humans , Infertility, Female/etiology , Middle Aged , Stress, Physiological/complications , Stress, Physiological/metabolism , Up-Regulation
5.
Br J Rheumatol ; 32(10): 908-10, 1993 Oct.
Article in English | MEDLINE | ID: mdl-7691368

ABSTRACT

Behçet's disease (BD) has features consistent with an immunopathogenic mechanism. We tested 23 patients with BD and 139 normal controls for autoantibodies to nuclear, cardiolipin and smooth muscle antigens using indirect immunofluorescence, immunodiffusion, Western blots and an enzyme immunosorbent assay. Serum immunoglobulin G, M and A levels were measured by standard radial immunodiffusion techniques. The prevalence of the following autoantibodies was raised in patients with BD compared with the control group: ANA on rodent (P < 0.05) and human (P < 0.01) substrates and smooth muscle antibody (P < 0.001). Anticardiolipin antibody was detected in one patient (GPL 23.1 U). Antibodies to the ribonucleoproteins Ro, La, Sm and RNP were not found. Levels of serum immunoglobulins G, M and A were elevated in BD compared with the controls and this was significant for immunoglobulin M (P < 0.05) and A (P < 0.001). These findings support the concept of a polyclonal B cell activation in BD.


Subject(s)
Autoimmunity , Behcet Syndrome/immunology , Adult , Autoantibodies/analysis , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Reference Values , Staining and Labeling
6.
Clin Exp Dermatol ; 18(5): 449-51, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8252769

ABSTRACT

A case of chilblain lupus erythematosus during pregnancy is described in a 28-year-old woman. Symptoms and signs were present by 8 weeks of her first pregnancy and had resolved by 10 days after delivery. The condition is discussed with particular emphasis on the relationship with pregnancy.


Subject(s)
Chilblains/etiology , Lupus Erythematosus, Cutaneous/etiology , Pregnancy Complications/etiology , Adult , Chilblains/drug therapy , Female , Humans , Lupus Erythematosus, Cutaneous/drug therapy , Prednisolone/therapeutic use , Pregnancy , Pregnancy Complications/drug therapy
7.
Br J Obstet Gynaecol ; 98(7): 680-4, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1883792

ABSTRACT

Serum samples from 71 patients with laparoscopically staged endometriosis and from 109 age-matched non-pregnant control women were tested for antibodies to nuclear, phospholipid, smooth muscle and sperm antigens. Immunoglobulin G, M and A and complement components C3 and C4 were measured. Prevalence of the following autoantibodies was statistically significantly greater in women with endometriosis than in the control group: antinuclear antibodies, antibodies to ribonucleoproteins, smooth muscle antibodies, lupus anticoagulant and anticardiolipin antibody. Forty-one women with endometriosis (58%) had some type of autoantibody compared with 13 controls (12%). More women in the endometriosis group had IgG and IgM levels above the normal range. This was statistically significant for IgG in women with grade 3 and for IgM in those with grade 4 endometriosis, IgG levels were significantly higher in antibody-positive women with endometriosis than in the control group. Immunoglobulin and complement component levels tended to have a positive correlation with stage of disease.


Subject(s)
Antibodies/analysis , Endometriosis/immunology , Adolescent , Adult , Autoantibodies/analysis , Cardiolipins/immunology , Complement C3/analysis , Complement C4/analysis , Female , Fluorescent Antibody Technique , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Middle Aged , Muscle, Smooth/immunology , Spermatozoa/immunology
9.
J Autoimmun ; 4(1): 165-76, 1991 Feb.
Article in English | MEDLINE | ID: mdl-2031658

ABSTRACT

Congenital complete heart block (CCHB) is a rare but potentially fatal disease of infants born to mothers with autoimmune disease where maternal autoantibodies to Ro (SS-A) are thought to cross the placenta and damage fetal cardiac tissue. We have adopted a novel approach to demonstrate the localization and specificity of maternal autoantibodies deposited in fetal heart. We raised an anti-idiotype against maternal anti-La antibodies, which reacted strongly with the surface immunoglobulin on the myocardial fibres from a CCHB heart but not a control fetal heart of the same age. Maternal immunoglobulin eluted from the CCHB heart reacted with La (SS-B) by ELISA. Using monoclonal and affinity-purified antibodies to La and affinity-purified anti-Ro antibodies, both antigens were identified on the surface of the fibres of the affected heart. Surface co-expression of immunoglobulin, complement and Class II antigen, consistent with a local immune response, was also found. This is the first definitive demonstration of Ro and La antigens and specific maternal anti-La antibody and idiotype on the surface of myocardial fibres in CCHB. It suggests that induction of Ro and La antigens on the surface of myocardial fibres during fetal development may be critical in the localization of the specific autoantibodies and subsequent evolution of congenital complete heart block.


Subject(s)
Antibodies, Antinuclear , Autoantigens , Heart Block/congenital , RNA, Small Cytoplasmic , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Female , Fetal Heart/immunology , Heart Block/etiology , Heart Block/immunology , Humans , Immunoglobulin Idiotypes , Infant, Newborn , Male , Myocardium/immunology , Pregnancy , Pregnancy Complications/immunology , Ribonucleoproteins/immunology , SS-B Antigen
10.
Am J Obstet Gynecol ; 161(2): 377-9, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2669491

ABSTRACT

Serum samples from 41 patients suffering from unexplained infertility and 351 normal pregnant women were assayed for a range of autoantibodies by means of immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion, Western blots, and enzyme-linked immunosorbent assays. The prevalence of autoantibodies to smooth muscle, phospholipid, and nuclear antigens, the latter when detected by immunofluorescence, was elevated in women with infertility compared with normal pregnant women (p less than 0.001, less than 0.001, and less than 0.05, respectively). Antiviral antibodies were not detected. The reason for the high level of autoreactivity in infertile women is unclear, but smooth muscle and antiphospholipid antibodies may actively interfere with the reproductive process.


Subject(s)
Autoantibodies/analysis , Infertility, Female/immunology , Antibodies, Antinuclear/analysis , Antibodies, Viral/analysis , Female , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Immunologic Techniques , Muscle, Smooth/immunology , Phospholipids/immunology , Pregnancy/immunology , Ribonucleoproteins/immunology
12.
J Reprod Immunol ; 14(2): 115-23, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3236293

ABSTRACT

In 36 women with unexplained primary recurrent abortion, 13 with secondary unexpained recurrent abortion, 25 with primary unexplained infertility, 7 with secondary unexplained infertility and two groups of control women, autoantibodies to soluble cellular antigens were measured by Western blotting to a disaggregated HeLa cell antigen preparation, by counter immunoelectrophoresis and by indirect immunofluorescence. Using Western blotting the women with primary infertility and those with secondary recurrent abortion had a significantly higher prevalence of autoantibodies (P less than 0.01 in each case). This was not shown using the other methods. It is possible that these antibodies could be causally related to the pathology of the conditions studied.


Subject(s)
Abortion, Habitual/immunology , Antigens/immunology , Autoantibodies/immunology , Infertility, Female/immunology , Adult , Blotting, Western , Female , HeLa Cells/immunology , Humans , Pregnancy , Solubility
14.
Br J Rheumatol ; 27(2): 128-32, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3284603

ABSTRACT

The prevalence of autoantibodies to ribonucleoprotein antigens in cases of congenital heart block was established using immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion and Western blots. All of 35 mothers of babies with congenital heart block, none of five mothers of babies with other types of heart block, 10 of 29 women with connective tissue disease but no babies with heart block, four of 445 normal pregnant women and two of 109 healthy nonpregnant women had either Ro (SS-A) or La (SS-B) antibodies. Of 15 babies with congenital heart block, 10 of 10 who were less than 3 months old possessed antibody. Antibody titres in affected but not in normal infants were lower compared with their mothers' titres, suggesting deposition of antibodies in the baby's tissues. The findings indicate that placental transfer of anti-Ro (SS-A) or anti-La (SS-B) is essential for development of congenital complete heart block.


Subject(s)
Antibodies, Antinuclear/analysis , Heart Block/congenital , Counterimmunoelectrophoresis , Female , Fluorescent Antibody Technique , Heart Block/immunology , Humans , Infant , Maternal-Fetal Exchange , Pregnancy , Pregnancy Outcome , Ribonucleoproteins/analysis
15.
N Engl J Med ; 315(11): 667-72, 1986 Sep 11.
Article in English | MEDLINE | ID: mdl-3018560

ABSTRACT

An immunologic basis for congenital heart block has been proposed previously. To investigate the association between congenital heart block and maternal antibodies capable of crossing the placenta, we used immunofluorescence to examine serum samples from 41 mothers and 8 affected children, together with serum from controls, for antibodies to fetal cardiac tissue. Twenty-one mothers (51 percent) had IgG antibody reactive with fetal heart tissue, as compared with only 9 of 94 controls (10 percent; P less than 0.001). Three of 8 affected babies, but none of 50 healthy babies, had similar antibodies. The antibodies reacted with all myocardial tissue and were not directed specifically to the conduction system. They also reacted with other fetal tissues and could be distinguished from nuclear and smooth-muscle autoantibodies. We also observed a higher occurrence of antibodies to cytomegalovirus, but not to Epstein-Barr virus, in these mothers. Autopsy specimens from babies with congenital heart block examined by immunoperoxidase staining showed deposition of immunoglobulin and complement components in all cardiac tissues. These findings strengthen the case implicating immune reactivity related to maternal antibody in the development of some but not all cases of congenital heart block.


Subject(s)
Autoantibodies/analysis , Fetal Heart/immunology , Heart Block/congenital , Maternal-Fetal Exchange , Antibodies, Antinuclear/analysis , Antibodies, Viral/analysis , Cytomegalovirus/immunology , Female , Fetal Diseases/immunology , Heart Block/immunology , Herpesvirus 4, Human/immunology , Humans , Immunoglobulin G/analysis , Infant , Infant, Newborn , Pregnancy
16.
Arch Biochem Biophys ; 240(2): 689-97, 1985 Aug 01.
Article in English | MEDLINE | ID: mdl-2992381

ABSTRACT

Proton nuclear magnetic resonance spectra are reported for cytochrome cd1 from Pseudomonas aeruginosa (ATCC 19429) in several forms including complexes of the ferricytochrome with cyanide, azide, and fluoride, a quasi-apo form in which the noncovalently associated heme d1 has been removed but the covalently bound heme c is retained, and the reduced state of both native and the quasi-apo forms. Comparisons are made to the previously reported spectrum of ferricytochrome cd1. The following points are made. The spectra of the azide and fluoride complexes and the ferric quasi-apo form show perturbation of resonances assignable to the site of heme d1, and leave relatively unperturbed resonances assignable to the site of heme c. The heme d1 associated resonances are at 46.0, 35.4, 23.3, 17.5, -2.9, and 16 ppm, and the heme c associated resonances are at 42.0, 33.7, 15.0, 13.9, -7.5, -14, and -33 ppm in native ferricytochrome cd1. The similarity of the hyperfine resonances of the ferric quasi-apo from to the heme c resonances of intact ferricytochrome cd1 is evidence that removal of heme d1 leaves the heme c binding site relatively unaltered. Linewidths and relaxation times suggest that the relaxation times of the unpaired electron spins of the ferric hemes c and d1 are on the same order of magnitude. Although it is paramagnetic, ferrocytochrome cd1 does not demonstrate an experimentally detectable hyperfine shifted spectrum under present conditions. Possible reasons for this are discussed. The presence of a narrow resonance at -2.8 ppm in both ferrocytochrome cd1 and the reduced state of the quasi-apo form suggests that methionine may be a ligand to heme c.


Subject(s)
Electron Transport Complex IV , Nitrite Reductases , Azides , Cyanides , Cytochromes , Fluorides , Magnetic Resonance Spectroscopy , Pseudomonas aeruginosa/enzymology
18.
J Biol Chem ; 259(24): 15089-93, 1984 Dec 25.
Article in English | MEDLINE | ID: mdl-6549007

ABSTRACT

The configuration of the substituents around the macrocycle core has been determined for acrylochlorin, the reduced porphyrin that is the iron-free form of heme d1. This has been accomplished by two independent techniques. Nuclear Overhauser enhancements on the proton resonances of acrylochlorin d3-methyl ester were measured to determine nearest-neighbor substituents and mesoprotons. A lanthanide shift reagent, tris-(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-di onato) europium(III), was found to bind in the vicinity of the carbonyl oxygens of the propionate and acrylate methyl esters. Differential chemical shift effects on the proton resonances of acrylochlorin provided evidence on relative distances from the lanthanide-binding site. Since the substituents are constrained along the circumference of the macrocycle, this provided information on configuration. Assuming that the dominant mechanism for spin-lattice relaxation in acrylochlorin in deuterated chloroform solution is proton dipole-dipole interaction, measured values of spin-lattice relaxation times could be interpreted as being consistent with the proposed configuration. The configuration bears sufficient similarity to that of protoporphyrin IX so that a common nomenclature may be used (Smith K. M. (ed) (1975) Porphyrins and Metalloporphyrins, pp. 3-5, Elsevier/North-Holland Biomedical Press, Amsterdam). The deduced configuration of the acrylochlorin methyl ester is: 1-methyl, 1-hydroxymethyl, 2-methyl, 2-hydroxymethyl, 3-methyl formate, 4-methyl formate, 5-methyl, 6-methyl propionate, 7-methyl acrylate, 8-methyl. The naturally occurring heme d1 has free carboxylic acids at the 3-, 4-, 6-, and 7-positions.


Subject(s)
Heme/analysis , NADH, NADPH Oxidoreductases/metabolism , Nitrite Reductases/metabolism , Porphyrins/pharmacology , Protoporphyrins/pharmacology , Binding Sites , Cytochrome c Group , Cytochromes/metabolism , Kinetics , Magnetic Resonance Spectroscopy/methods , Protein Binding , Thiobacillus/metabolism
19.
J Inorg Biochem ; 22(1): 21-32, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6092534

ABSTRACT

A high molecular-weight c-type cytochrome was purified from Alcaligenes faecalis ATCC 8750. Its weight was 40,000 daltons by sodium dodecyl sulfate-gel electrophoresis. Heme content was determined to be one heme per 40,000 daltons. Proton nuclear magnetic resonance-NMR-spectroscopy determined that the ferrous form is low spin. The detection of a methyl resonance at -3 ppm in the ferrous form indicated that methionine is a heme ligand in this state. The NMR spectrum of the ferric form at pH 7.2 revealed hyperfine shifted methyl resonances at 67.79, 63.17, 57.71, and 50.46 ppm. The large downfield shifts observed are indicative of high spin character. The ferric spectrum was pH-sensitive, indicating two pH-linked structural transitions with estimated pKs at 6.0 and 10.5. The first is interpreted as due to the ionization of a heme propionate. The second is interpreted as the acquisition of a strong field ligand and the subsequent conversion to a low spin ferric form. The ferricytochrome did not form complexes with cyanide, azide, or fluoride at pH 5.2 or 7.9.


Subject(s)
Alcaligenes/analysis , Cytochrome c Group , Magnetic Resonance Spectroscopy , Cytochrome c Group/isolation & purification , Ferric Compounds , Ferrous Compounds , Hydrogen-Ion Concentration , Molecular Weight , Oxidation-Reduction , Spectrophotometry
20.
Biochemistry ; 23(15): 3526-33, 1984 Jul 17.
Article in English | MEDLINE | ID: mdl-6087896

ABSTRACT

The 1H NMR spectra of ferri- and ferro-cytochrome c-550 from Paracoccus denitrificans (ATCC 13543) have been investigated at 300 MHz. The ferri-cytochrome c-550 shows hyperfine-shifted heme methyl resonances at 29.90, 29.10, 16.70, and 12.95 ppm and a ligand methionyl methyl resonance at -15.80 ppm (pH 8 and 23 degrees C). Four pH-linked structural transitions were detected in spectra taken as a function of pH. The transitions have been interpreted as loss of the histidine heme ligand (pK less than or equal to 3), ionization of a buried heme propionate (pK = 6.3 +/- 0.2), displacement of the methionine heme ligand by a lysyl amino group (pK congruent to 10.5), and loss of the lysyl ligand (pK greater than or equal to 11.3). The temperature behavior of hyperfine-shifted resonances was determined. Two heme methyl resonances (at 16.70 and 12.95 ppm) showed downfield hyperfine shifts with increasing temperature. The cyanoferricytochrome had methyl resonances at 23.3, 20.1, and 19.4 ppm. NMR spectroscopy did not detect the formation of a complex with azide. The second-order rate constant for electron transfer between ferric and ferrous forms was determined to be 1.6 X 10(4) M-1 s-1. Heme proton resonances were assigned in both oxidation states by cross-saturation and nuclear Overhauser enhancement experiments. Spin-coupling patterns in the aromatic region of the ferro-cytochrome spectrum were investigated.


Subject(s)
Cytochrome c Group/metabolism , Paracoccus denitrificans/metabolism , Heme/analysis , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy/methods , Protein Conformation
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