1/9. properdin deficiency in a large Swiss family: identification of a stop codon in the properdin gene, and association of meningococcal disease with lack of the IgG2 allotype marker G2m(n).properdin deficiency was demonstrated in three generations of a large Swiss family. The concentration of circulating properdin in affected males was < 0.1 mg/l, indicating properdin deficiency type I. Two of the nine properdin-deficient males in the family had survived meningitis caused by neisseria meningitidis serogroup B without sequel. Two point mutations were identified when the properdin gene in one of the properdin-deficient individuals was investigated by direct solid-phase sequencing of overlapping polymerase chain reaction (PCR) products. The critical mutation was found at base 2061 in exon 4, where the change of cytosine to thymine had generated the stop codon TGA. The other mutation was positioned at base 827 in intron 3. The stop codon in exon 4 was also demonstrated by standard dideoxy sequencing in three additional family members. The question was asked if genetic factors such as partial C4 deficiency and IgG allotypes could have influenced susceptibility to meningococcal disease in the family. No relationship was found between C4 phenotypes and infection. Interestingly, the two properdin-deficient males with meningitis differed from the other properdin-deficient persons in that they lacked the G2m(n) allotype, a marker known to be associated with poor antibody responses to T-independent antigens. This implies that the consequences of properdin deficiency might partly be determined by independent factors influencing the immune response.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/9. vaccination responses to capsular polysaccharides of neisseria meningitidis and haemophilus influenzae type b in two C2-deficient sisters: alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG.meningitis caused by neisseria meningitidis serogroup W-135 was diagnosed in a 14-year-old girl with a history of neonatal septicemia and meningitis caused by group B streptococci type III. C2 deficiency type I was found in the patient and her healthy sister. Both sisters were vaccinated with tetravalent meningococcal vaccine and a conjugate haemophilus influenzae type b vaccine. Three main points emerged from the analysis. First, vaccination resulted in serum bactericidal responses demonstrating anticapsular antibody-mediated recruitment of the alternative pathway. Second, addition of C2 to prevaccination sera produced bactericidal activity in the absence of anticapsular antibodies, which suggested that the bactericidal action of antibodies to subcapsular antigens detected in the sera might strictly depend on the classical pathway. A third point concerned a previously unrecognized type of blocking activity. Thus, postvaccination sera of the healthy sister contained IgG that inhibited killing of serogroup W-135 in C2-deficient serum, and the deposition of C3 on enzyme-linked immunosorbent assay plates coated with purified W-135 polysaccharide. Our findings suggested blocking to be serogroup-specific and dependent on early classical pathway components. Retained opsonic activity probably supported post-vaccination immunity despite blocking of the bactericidal activity. The demonstration of functional vaccination responses with recruitment of alternative pathway-mediated defense should encourage further trial of capsular vaccines in classical pathway deficiency states.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/9. The varied clinical presentations of meningococcal infection.The clinical presentation of neisseria meningitidis may include bacteremia, septic shock, or meningitis. The polysaccharide capsule of the organism appears to be the major determinant and is necessary for specific immunity. Colonization of the nasopharynx is required for invasion, and persons with complement component deficiencies are particularly at risk of infection. The organism can be detected by culture of blood or spinal fluid, or by antigen detection in spinal fluid. Prompt therapy with penicillin g is necessary for a good outcome. The occurrence of secondary cases requires that prophylactic therapy be administered to close contacts of index cases. The cases presented herein illustrate a variety of manifestations of meningococcal infection, and all of the patients initially were seen in primary care settings. It is important for physicians to be vigilant for these infections so that appropriate therapy may be instituted rapidly.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/9. Complete and partial deficiencies of complement factor d in a Dutch family.A young man suffering from recurrent Neisseria infections was shown to lack detectable serum complement factor d hemolytic activity. Addition to the patient's serum of purified factor D to a final concentration of 1 microgram/ml resulted in full restoration of the activity of the alternative pathway. Using an enzyme-linked immunosorbent assay, it was shown that the patient's serum did not contain measurable amounts of factor D antigen either. The sister, the father, as well as the parents of the mother had factor D levels within the normal range, and the factor D level of the mother was decreased. The capacity of the patient's serum, at concentrations up to 5%, to promote phagocytosis of escherichia coli by normal human granulocytes was low when compared to normal serum. Substitution of the patient's serum with purified factor D resulted in a full restoration of opsonic activity. This study describes the first complete deficiency of factor D, and demonstrates its possible relation to recurrent Neisseria infections.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/9. Meningococcal disease in congenital absence of the fifth component of complement.We describe a family in which 2 brothers had meningococcal infection, 1 of them twice. Their parents were first degree cousins. The brothers showed a complete, isolated deficiency of C5, both antigenic and functional. The parents had half-normal values, and the data are compatible with an inherited C5 deficiency where the defect is transmitted as an autosomal codominant trait.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/9. complement c8 deficiency with recurrent meningococcemia: examination of meningococcal opsonization.A 10 year old girl presented with recurrent febrile episodes over 2 months. A non-typable strain of neisseria meningitidis was grown from blood cultures on three occasions. She was found to lack functional C8 activity in serum but material with C8 antigenic activity was present. The opsonic activity of the C8 deficient serum for N. meningitidis was equivalent to that of normal controls.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/9. Recurrent meningococcal meningitis due to partial complement defects and poor anti-meningococcal antibody response.An otherwise healthy young man had three episodes of meningococcal meningitis within three years. The last episode was caused by group A, and occurred four weeks after the patient received group A vaccine, thus representing one of the very few failures of this vaccine. The specific susceptibility to meningococcal infections was connected with half-normal levels of several components of the complement system (C3, C4, C9, factor B, properdin), and reduced antibody responses to group A and group C meningococcal polysaccharides, but not to several other polysaccharide or protein antigens.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/9. Enzyme electrophoresis, sero- and subtyping, and outer membrane protein characterization of two neisseria meningitidis strains involved in laboratory-acquired infections.Two cases of laboratory-acquired infections due to neisseria meningitidis were suspected to have occurred in two French hospitals. The first case occurred shortly, i.e., 3 days, after one strain had been handled by a laboratory technician, and the link between this strain and the strain causing meningitis was easily established. In the second case, infection occurred 3 weeks after 10 strains had been handled by a technician. In this case, it was necessary to use high-resolution markers in order to establish the link between the infecting strain and 1 of the 10 strains handled. The antigenic formulae of the two infecting strains (serogroup:serotype:subtype) were, respectively, C:NT:P1.12 and B:2a:P1.2. Outer membrane protein profile analysis and multilocus enzyme electrophoresis unequivocally confirmed the identity of the respective strains.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/9. Post immunization Hib antigen detection in the CSF of a patient with meningococcal meningitis.We report a case of meningococcal meningitis where the cerebrospinal fluid was negative for neisseria meningitidis but positive for Haemophilus influenzae type b by rapid antigen detection test. We believe that this was due to prior immunization with haemophilus influenzae type b vaccine. We recommend caution in interpretation of the rapid antigen detection tests especially in patients who had been vaccinated against organisms screened by these tests.- - - - - - - - - - ranking = 6keywords = antigen (Clic here for more details about this article) |