Primary immunodeficiency register, United Kingdom: update 1992.
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Adolescent↗
Biomedical subjects
H C Gooi
Publications and source records attributed to H C Gooi.
The effect of non-steroidal anti-inflammatory drugs on faecal flora and bacterial antibody levels in rheumatoid arthritis.
The faecal flora and bacterial antibody levels of 22 patients with active rheumatoid arthritis (RA) were compared with those of 26 patients with osteoarthritis (OA) undergoing comparable treatment with non-steroidal anti-inflammatory drugs (NSAIDs), and a further 22 patients with OA who were not receiving NSAIDs. Faecal counts of Clostridium perfringens were significantly higher in the RA patient group and in those OA patients receiving NSAIDs, compared with those OA patients not taking NSAIDs (P = 0.032, P = 0.0004 respectively). Total aerobic and anaerobic counts were, however, identical in all three groups. Levels of serum IgA antibody to the alpha toxin of Cl. perfringens were higher in the RA group and in the OA group taking NSAIDs than in OA patients not taking NSAIDs (P = 0.011, P = 0.055). Serum IgG antibody to alpha toxin was higher in the RA group than in OA patients both on and off NSAIDs (P = 0.019, P = 0.0072) and also a group of normal controls (P = 0.032). These results suggest that the increased faecal counts of Cl. perfringens together with the associated increased antibody levels seen in this and previous studies are more likely to result from NSAID therapy used to treat the disease than from a disease specific change in bowel flora.
Adult↗
Abnormal CD45R expression in patients with common variable immunodeficiency and X-linked agammaglobulinaemia.
This study has investigated the patterns of membrane 2H4 (CD45RA) and UCHL1 (CD45RO) expression by CD4+ and CD8+ lymphocyte subpopulations in 10 adults and seven children with common variable immunodeficiency (CVI) and X-linked hypogammaglobulinaemia (XLA). Of the 10 adults (CVI, n = 8; XLA, n = 2), only one with a diagnosis of CVI showed normal CD45R expression. For the remaining seven adult CVI patients the abnormal CD45R profiles were primarily associated with CD4+ lymphocytes in three and CD8+ lymphocytes in four. Specific increases in CD45RA- CD45RO+ fractions were found in four CVI patients and in all of these there was a concomitant reduction in circulating CD19+ B-cell numbers. Two of the CVI cases were identical twin sisters and both had the same CD45R abnormality. The two adults with XLA also showed abnormal CD45R expression (increased CD45RA+ CD45RO- components) but of particular note, in view of the fact that these were brothers, one was associated with the CD4+ subpopulation and the other with the CD8+ fraction. Similar analyses for the paediatric group revealed, in distinct contrast to the adult patients, no significant abnormalities of CD45R expression suggesting that these defects may not become apparent until a later age. Further investigations of in vitro lymphocyte proliferation (PHA and PWM) in the eight adults with CVI showed a significant correlation between abnormal responses and disordered CD45R expression. It is proposed that these abnormal patterns of CD45R expression by lymphocyte subpopulations in CVI and XLA may be of fundamental importance with respect to the pathogenesis of these particular immunodeficiencies.
Adolescent↗
Differences in the characteristics of human monoclonal and polyclonal anti-D as revealed by immunochemical investigations: human monoclonal antibodies share specificities with natural antibodies.
To determine the basis of the tissue cross-reactions shown by some human monoclonal anti-Rh D antibodies, we have investigated the tissue reactivities of 48 further human monoclonal antibodies (mAb) against D and other Rh antigens, and compared them with those of normal and anti-D sera and immunoglobulin preparations, and affinity-purified polyclonal anti-D antibodies. Although we were unable to detect any tissue reactivities associated with the D-binding fraction of polyclonal antisera or prophylactic immunoglobulin, the non-erythroid cell types identified by the tissue-reactive human anti-Rh mAb of both IgM and IgG class were those recognized by antibodies present in both normal and anti-D sera. These results indicate: (a) that the tissue specificities of human anti-Rh mAb are similar to those of natural antibodies, and (b) that there are immunochemical differences between polyclonal and monoclonal anti-D antibodies, at least of IgG class, which may be relevant to the use of the latter in the prevention of haemolytic disease of the new-born by immune prophylaxis.
Animals↗
Systemic lupus erythematosus presenting with myelofibrosis.
The 20-year-old girl we describe presented with myelofibrosis and systemic lupus erythematosus (SLE), which initially responded to treatment with corticosteroids but during a relapse 9 months later a bone marrow biopsy revealed no improvement in her myelofibrosis. As the cytotoxic treatments used to treat severe SLE may be associated with bone marrow suppression, it is important to consider the possibility of myelofibrosis complicating SLE, which, even when it is a presenting feature, may not readily respond to corticosteroids. When this girl was subsequently treated with high dose steroid and azathioprine her myelofibrosis went into remission.
Adrenal Cortex Hormones↗
Variant CD45R expression with autosomal dominant inheritance affects both helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) T cell populations.
The differential expression of various membrane CD45R isoforms by normal lymphocyte populations is known to be closely associated with distinct immunoregulatory functions. Abnormal patterns of CD45R expression have been reported in patients with common variable immunodeficiency and HIV infection, and recent evidence has suggested the possibility that one type of variant CD45R expression may be inheritable. By multiple colour flow cytometry, we studied the immunological characteristics of CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in a family with variant CD45R expression over three generations. This variant pattern of CD45R expression was shown to affect both CD4+ and CD8+ lymphocyte populations in individual family members and was immunologically characterized by a failure of the normal reciprocal expression of the CD45RA and CD45RO isoforms. Family studies also revealed that this trait had an autosomal dominant mode of inheritance and, in the heterozygous state, appeared not to be associated with major clinical abnormalities. The different isoforms of CD45 show distinct patterns of expression during lymphocyte ontogeny and activation, and these patterns appear to closely reflect function. Despite their diverse immunological roles, our finding that both CD4+ and CD8+ T cells in affected family members showed the same defect suggests a common regulatory mechanism(s) for both these lymphocyte populations. The recognition of this abnormality, particularly in homozygous individuals, will be of great importance in understanding the role of these molecules in immune function and disease.
Adolescent↗
Prophylactic intravenous immunoglobulin in pre-term infants: a controlled trial.
Sixty-six pre-term infants of less than 30 weeks gestation consecutively admitted to either of two neonatal intensive care units were randomized to receive routine intensive care only or prophylactic intravenous immunoglobulin, 200 mg/kg body weight at 3-weekly intervals in addition to routine intensive care. Eleven babies, 6 in the control group and 5 in the treatment group, were withdrawn from the trial due to early death from extreme prematurity (7 babies), early return to the referring hospital (3 babies), and elective treatment with intravenous immunoglobulin for severe congenital septicaemia (1 baby). Of the 55 who remained in the trial, significantly fewer babies in the treatment group had infection, 8 compared to 17 (p = 0.01). This difference was not significant when blood-culture-proven septicaemia only was considered, 8 compared to 14 (p = 0.09). Twenty-seven (84%) of 32 blood-culture-positive episodes of infection were caused by coagulase-negative staphylococci. Serum IgG was significantly higher with treatment and achieved levels comparable to those of normal full-term babies at the same post-natal age.
Bacterial Infections↗
500-MHz 1H-n.m.r. and conformational studies of fucosyloligosaccharides recognised by monoclonal antibodies with specificities related to Le(a), Le(b), and SSEA-1.
500-MHz 1H-n.m.r. spectroscopy has been used to examine several fucosylated oligosaccharides in studies to characterise carbohydrate antigenic determinants recognised by monoclonal antibodies. Reduction of the oligosaccharides to give additional variants for analysis showed that oligosaccharides having an alpha-L-fucosyl group linked to the reducing end residue have markedly different chemical shifts, and in some instances different antigenic activity, compared to their alditols. This information was incorporated into space filling molecular models of the oligosaccharides in order to predict the topography of atoms recognised by the antibody combining sites. These studies are an intermediate stage in the full characterisation of oligosaccharide conformation and molecular recognition by methods which accurately determine torsional angles and through-space internuclear distances.
Antibodies, Monoclonal↗
The immunochemistry of some blood group antigens. Relation to erythrocyte membrane structure and to hemagglutination.
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Blood Group Antigens↗
Detection of somatic changes in human cancer DNA by DNA fingerprint analysis.
Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 cases. The changes included alterations in the relative intensities of hybridising DNA fragments, and, in three cases of cancers of gastrointestinal origin, the appearance of novel minisatellite fragments not seen in the corresponding constitutional DNA. The results of this preliminary study suggests that DNA fingerprint analysis provides a useful technique for identifying somatic changes in cancers.
Breast Neoplasms↗
Viral challenge in leprosy: viraemia, interferon, and specific antibody production.
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Antibody Formation↗
Differing reactions of monoclonal anti-A antibodies with oligosaccharides related to blood group A.
Inhibition radioimmunoassays with blood group A-related oligosaccharides have been used to investigate the specificities of six monoclonal anti-A antibodies, three of which had been intentionally generated by immunization of mice with blood group A erythrocytes and A-active blood group substance, and three were incidentally produced following immunization of mice with human tonsil cell membranes or a human colon cancer cell line. By hemagglutination, these antibodies are highly specific for human blood group A erythrocytes. However, they differ from one another in their reaction patterns with mono- and difucosyl A antigen structures and the corresponding afucosyl sequences on Type 1 and Type 2 backbone structures. The six antibodies, together with four previously characterized anti-A monoclonal antibodies (originally raised against the receptor for epidermal growth factor) have been classified into five groups. The first two groups consist of antibodies with broad specificities for A-related structures. There are five antibodies in the first group (TL5, 29.1, A17/3D1, MH2/6D4, and MH1/5D1) reacting to varying degrees with the mono- and difucosyl A antigen structures on either type of backbone sequence. In the second group are two antibodies (A15/3D4 and A15/3D3) which are difficult to inhibit with the oligosaccharides tested, but they reacted best with monofucosyl A structure on either type of backbone. Each of the remaining three antibodies had a distinct and more restricted reaction pattern, with a specificity for the difucosyl A antigen on both types of backbone (antibody EGR/G49) or the Type 1-based mono- and difucosyl A antigen structures (antibody MAS 016c) or the Type 2-based monofucosyl A antigen structure (antibody 455). The reactions of four of the antibodies with N-acetylgalactosamine or with oligosaccharides containing the afucosyl sequence GalNAc alpha 1-3Gal suggest that they may react with certain glycoconjugates with alpha-N-acetylgalactosaminyl termini ("A-like" structures) that are unrelated to the products of the blood group A gene-specified alpha-N-acetylgalactosaminyl-transferase. Knowledge of the differing reactions of these monoclonal antibodies is important for interpreting their reactions with glycoproteins and glycolipids of diverse origins.
ABO Blood-Group System↗
Novel antigenic specificity involving the blood group antigen, Lea, in combination with onco-developmental antigen, SSEA-1, recognized by two monoclonal antibodies to human milk-fat globule membranes.
Two monoclonal antibodies to human milk-fat globule membranes, which recognize an epithelial antigen designated MAM-3c, were found to bind strongly to epithelial glycoproteins derived from non-secretors. Further investigations, using purified glycoproteins and structurally defined oligosaccharides, established that the optimal antigenic structure for both antibodies involves the Type 1 based blood group antigen, Lea, in combination with the Type 2 based onco-developmental antigen, SSEA-1, (Formula: see text) as in lacto-N-difucohexaose II. The antibodies may also react with the corresponding monofucosyl structures lacking the 3- or 4- linked fucose residues and to a lesser extent with the afucosyl tetrasaccharide sequence as in lacto-N-tetraose. The Lea and SSEA-1 antigens are known to occur on human epithelial glycoproteins. However, this is the first report of an antigenic specificity involving a combination of the Type 1 and Type 2 based fuco-oligosaccharides and occurring on epithelial glycoproteins.
Antibodies, Monoclonal↗
Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens.
Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. Their structures, in order of abundance, were: (Formula: see text).
Animals↗
The carbohydrate specificities of the monoclonal antibodies 29.1, 455 and 3C1B12 to the epidermal growth factor receptor of A431 cells.
Sixteen hybridoma-derived antibodies to the epidermal growth factor receptor of A431 cells were studied with respect to their reactions with blood group-related carbohydrate structures. Twelve of these were assessed as recognizing carbohydrate determinants on the basis of their immunostaining of reference blood group substances on nitrocellulose paper. Three of these antibodies were further investigated by inhibition of binding assays with glycoproteins and structurally defined oligosaccharides or by haemagglutination of erythrocytes before and after treatment with endo-beta-galactosidase. Two of the antibodies, 29.1 and 455, were shown to have blood group A-related specificities which differed from one another and from those of monoclonal anti-A antibodies described previously. The third antibody, 3C1B12, which was shown to recognize a determinant based on alpha 1----3 fucosylated Type 2 chains on linear and branched backbone sequences, also differs from previously described monoclonal antibodies of 3-fucosyl-N-acetyllactosamine type, such as anti-SSEA-1 (anti-mouse embryo) and several antibodies to human myeloid cells. While these antibodies are invaluable in providing structural information on the carbohydrate chains of the receptor glycoprotein and should help to elucidate their functions, their use as 'anti-receptor' reagents in cell biology will be influenced by the knowledge that the determinants they recognize are shared by other glycoproteins and glycolipids of diverse cell types.
Animals↗
Monoclonal antibody (EGR/G49) reactive with the epidermal growth factor receptor of A431 cells recognizes the blood group ALeb and ALey structures.
The carbohydrate specificity of the monoclonal antibody EGR/G49, raised against the epidermal growth factor (EGF) receptor of A431 cells, has been investigated by assessing its interactions with glycoproteins and erythrocytes derived from individuals of known blood group ABH, Lewis and secretor types, and by inhibition of binding assays using structurally defined oligosaccharides. The results indicate that this antibody reacts with the difucosylated blood group structures ALeb and ALey: (formula; see text) This antibody differs from the previously described anti-EGF receptor antibody. TL5, which is directed at the terminal blood group A trisaccharide structure and reacts poorly with the ALeb/Ley structures. Since both antibodies were selected for their reactivities with the receptor for EGF, their specificities provide evidence for the presence of both the mono- and difucosylated blood group A structures on the receptor glycoprotein. These antibodies will be invaluable in the studies of the distribution and the roles of blood group related carbohydrate structures in the organisation and function of the EGF and other receptor systems.
ABO Blood-Group System↗
Differences in the fine specificities of monoclonal (Class A) antibodies to human myeloid cells.
Among 13 monoclonal antibodies to human myelomonocytic cells, six could be assigned to a group designated Class A with the following properties: (a) they react almost exclusively with granulocytes among cells of the peripheral blood, (b) they resemble the previously described anti-granulocyte antibodies, VEP8 and VEP9, and the anti-mouse embryo, anti-SSEA-1, in their strong reactions with human meconium glycoproteins and ovarian cyst mucins of non-secretor type and (c) they recognize the carbohydrate antigen 3-fucosyl-N-acetyllactosamine (alpha 1----3fucosylated Type 2 blood group chains). The binding of these anti-myeloid antibodies is more strongly inhibited by lacto-N-fucopentaose III than by the trisaccharide-fucosyl-N-acetyllactosamine, in contrast to anti-SSEA-1 which is more strongly inhibited by the trisaccharide. These observations suggest that the myeloid Class A antibodies recognize additional determinants on the neolacto (Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4) backbone of the pentasaccharide which occurs on the glycoproteins and glycolipids of myeloid cells. However, no two of the anti-myeloid antibodies were identical in their inhibition patterns with the glycoproteins and the two oligosaccharides. They also differed in their cellular reactivities, for example, the proportion of cells in the K-562 cell line reacting with each antibody ranged from 15-57%.
Antibodies, Monoclonal↗
Cell interactions in preimplantation embryos: evidence for involvement of saccharides of the poly-N-acetyllactosamine series.
Roles of cell surface carbohydrates containing the 3-fucosyl-N-acetyllactosamine and poly-N-acetyllactosamine sequences (SSEA-1 and I antigens, respectively) in the compaction of mouse embryos have been investigated using the endo-beta-galactosidase of Bacteroides fragilis to modify the surface of cleavage-stage embryos. Treatment with this enzyme abolished SSEA-1 activity and diminished I antigen activity on the embryonic cell surface. Embryos cultured in the presence of endo-beta-galactosidase from the 2- to 4-cell stage onwards, or treated with the enzyme at the compacting 8-cell stage, continued to compact and proceeded to form blastocysts at the normal rate. However, when compacted 8- to 16-cell embryos were experimentally decompacted in calcium-free medium, treated for 1 h with endo-beta-galactosidase and returned to normal culture medium, the time taken for 50% of the embryos to recompact was prolonged five-fold. There was an even greater delay if these embryos were maintained in culture medium containing the enzyme. Blastocysts were eventually formed under both conditions. Thus, endo-beta-galactosidase did not affect compaction unless the embryos were first decompacted. On the assumption that recompaction and de novo compaction occur by similar mechanisms, we propose that carbohydrate-binding molecules are involved which have high affinities for poly-N-acetyllactosamine structures and protect them from digestion by endo-beta-galactosidase.
Animals↗