Low Serum Immunoglobulin Research Articles

A minimally hypomorphic mutation in Btk resulting in reduced B cell numbers but no clinical disease

Reduced B cell numbers and a mutation in Btk are considered sufficient to make the diagnosis of X-linked agammaglobulinaemia. In the process of conducting family studies, we identified a 58-year-old healthy man with an amino acid substitution, Y418H, in the adenosine-5'-triphosphate binding site of Btk. Immunofluorescence studies showed that this man had 0.85% CD19+ B cells (normal 4-18%) in the peripheral circulation and his monocytes were positive for Btk. He had borderline low serum immunoglobulins but normal titres to tetanus toxoid and multiple pneumococcal serotypes. To determine the functional consequences of the amino acid substitution, a Btk- chicken B cell line, DT40, was transfected with expression vectors producing wild-type Btk or Y418H Btk. The transfected cells were stimulated with anti-IgM and calcium flux and inositol triphosphate (IP3) production were measured. Cells bearing the mutant protein demonstrated consistently a 15-20% decrease in both calcium flux and IP3 production. These findings indicate that even a modest decrease in Btk function can impair B cell proliferation or survival. However, a mutation in Btk and reduced numbers of B cells are not always associated with clinical disease.

Low Serum Immunoglobulin G2 Levels in Infancy Can Be Transient

The immunoglobulin G2 subclasses contain predominantly antipolysaccharide antibodies. It was therefore believed intuitively that low immunoglobulin G2 levels could predispose individuals to infections with encapsulated bacteria. Although many reports initially supported this notion, more recent studies challenged it. Regardless of the biological significance, the natural history of low immunoglobulin G2 levels has not been carefully studied. We studied the outcome of low serum immunoglobulin G2 subclass levels in children. Thirteen patients who were referred because of recurrent infections were found to have low immunoglobulin G2 levels. Laboratory evaluation at presentation and follow-up visits included total serum immunoglobulins, immunoglobulin subclasses, and specific antibodies to protein antigens and to pneumococcal vaccine. Low immunoglobulin G2 levels resolved completely within 0.6 years to 6 years (median: 1.5 years) in all patients. All 13 patients responded adequately to vaccination with protein antigens such as tetanus toxoid and polio as well as to immunization with pneumococcal vaccine. Four of 13 patients had a previous history of transient hypogammaglobulinemia, raising the possibility that the other cases may simply represent the tail end of this condition. We have demonstrated that low immunoglobulin G2 detected in early infancy and childhood is likely to resolve completely within several months and up to 6 years from the time of presentation.

The Relative Susceptibility of Mouse Strains to PulmonaryCryptococcus neoformansInfection Is Associated with Pleiotropic Differences in the Immune Response

CBA/J mice were highly susceptible to intratracheal (i.t.) Cryptococcus neoformans infection relative to BALB/c mice, while both strains were equally susceptible to intravenous (i.v.) infection. Increased susceptibility in i.t. infection was associated with higher brain CFU, lower serum immunoglobulin M (IgM) and IgG responses to glucuronoxylomannan (GXM), lack of IgE regulation during infection, and alveolar macrophage permissiveness to intracellular replication in vitro. In contrast, for BALB/c mice, relative resistance was associated with increased interleukin-12 (IL-12) and decreased IL-10 pulmonary levels. In CBA/J mice, relative susceptibility was associated with a decreased proportion of CD4+ and CD8+ T cells and an increase in macrophage percentage in pulmonary infiltrates. In contrast, no significant differences in these cytokines or cell recruitment were observed in the i.v. model, consistent with no differences in the survival rate. Passive antibody (Ab) protection experiments revealed a prozone effect in the BALB/c mice with i.v. infection, such that Ab efficacy decreased at higher doses. In the i.t. model using CBA/J mice, low Ab doses were disease enhancing and protection was observed only at high doses. Our results show (i) that differences in mouse strain susceptibility are a function of the infection model, (ii) that susceptibility to pulmonary infection was associated with macrophage permissiveness for intracellular replication, and (iii) that the efficacy of passive Ab in pulmonary infection is a function of dose and mouse strain. The results highlight significant differences in the pathogenesis of cryptococcal infection among inbred mice and associate their relative susceptibility with differences in numerous components of the innate and adaptive immune responses.

Serum proteins and paraproteins in women with silicone implants and connective tissue disease: a case–control study

Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case–control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants, were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and α1-globulin, α2-globulin, β-globulin, γ-globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51–6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation.

Interleukin‐18 Protects Splenectomized Mice from LethalStreptococcus pneumoniaeSepsis Independent of Interferon‐γ by Inducing IgM Production

The mechanism of the susceptibility of splenectomized mice to Streptococcus pneumoniae infection and the therapeutic effect of interleukin (IL)-18 were investigated. We demonstrated that, although S. pneumoniae challenge induced IL-12 production, it did not induce either interferon (IFN)-gamma or IL-18 production in mice with or without a splenectomy. Liver mononuclear cells stimulated with heat-killed S. pneumoniae but not with viable S. pneumoniae produced IFN- gamma in vitro. However, IL-18 pretreatment recovered the low serum immunoglobulin (Ig) M levels in splenectomized mice and completely inhibited mortality after S. pneumoniae infection without any IFN-gamma up-regulation. Injection of IgM from noninfected control mice into splenectomized mice before infection confirmed the essential role that IgM plays against S. pneumoniae infection. Therefore, low serum IgM levels but not a low IFN-gamma response in splenectomized mice cause lethality in S. pneumoniae infection, and IL-18 pretreatment protects them from infection by increasing IgM levels before infection.

Adult Asthma Severity in Individuals With a History of Childhood Asthma

Purpose of the Study. Childhood asthma has a range of outcomes in adulthood. This study sought to identify clinical features and exposures associated with persistence and severity of childhood asthma in adulthood. Study Population. Subjects had been previously enrolled in the Childhood Asthma Study, a double-blind, randomized, placebo-controlled trial designed to study the role of immunotherapy as an adjunct treatment. The 121 original study members, aged 5 to 12 years at the time of randomization, had moderate-to-severe asthma and had been followed for at least 1 year before enrollment. Evaluations performed during the original study included daily medication-symptom diaries, home allergen analysis, allergy skin testing, and methacholine challenges. The cohort had varied socioeconomic status, genders, and ethnicities. For this study an attempt was made to enroll all original participants. Methods. Eighty-five of the original subjects participated in the adult evaluation, underwent spirometry and inhalant allergy skin testing, and completed questionnaires regarding their interim medical history, asthma symptoms, and medications. Asthma severity was classified by using a modified version of the 1997 National Asthma Education and Prevention Program algorithm. Postbronchodilator spirometry was used for severity categorization. Subjects were categorized in the most severe category for which they qualified. Results. Thirteen (15.3%) of these young adults, aged 17 to 30 years, were in remission. Another 19 (22%) had only mild intermittent asthma. There were 12 (14%) with mild persistent asthma, 25 (29%) with moderate persistent asthma, and 16 (19%) with severe persistent disease. Subjects in remission, compared with subjects with mild intermittent or persistent asthma, had lower serum immunoglobulin E in childhood (412 vs 1136 vs 968 ng/mL, respectively) and fewer positive allergy skin tests (7 vs 9 vs 10, respectively, from a panel of 18 allergens). Subjects in remission also had milder childhood asthma, indicated by lower average daily medication usage scores and lower percentage of days on inhaled corticosteroids (13.7% vs 24.7% vs 40.9%). There was no association found between current asthma severity and childhood immunotherapy. Conclusions. The prognosis of childhood allergic asthma in adulthood is largely determined early in life. The degree of atopy seems to be a critical determinant of asthma persistence. Reviewer Comments. The authors point out that numerous studies of the natural history of asthma have suggested associations between childhood atopy and disease severity with risk of asthma persistence and severity in later childhood and adulthood. It remains to be seen whether there is any sort of intervention at a very early phase in the disease that will more favorably alter the course of asthma. Thus far, there are no compelling candidates.

Transient Hypogammaglobulinemia of Infancy: Twelve Years' Experience from Northern India

The clinical and immunological data of 8 patients diagnosed with transient hypogammaglobulinemia of infancy (THI) are presented and compared to published data. All patients diagnosed with THI (recurrent sinopulmonary infections, serum immunoglobulins < −2 S.D. for the age, apparently normal cellular immunity, and absence of evidence of other immunodeficiency syndromes) and registered in the Pediatric Rheumatology and Immunology Clinic of Post Graduate Institute of Medical Education and Research, Chandigarh were included in the study. Eight patients were diagnosed with THI. Mean age of onset of symptoms was 5.5 (±2.9) months. All patients had low serum immunoglobulin G (IgG) concentrations at admission. In 3 of the 8 (42.8%) cases, the serum IgA and IgM concentrations were also low. Respiratory infections were the most common presenting complaint. All children received prophylactic cotrimoxazole. The mean follow-up period was 23.6 months (range 10–38 months). Seven of the 8 patients became asymptomatic during follow up, and treatment was stopped at a mean age of 35.3 months. Serum IgG concentrations were normalized in all, except 2 patients, by 15–26 months. Serum IgA persisted to be low in 2 of 8 cases. Two of the 8 patients had severe pneumonia and were given intravenous immunoglobulin (IVIG) during the acute episode. THI is a relatively uncommon disorder and can only be diagnosed with certainty in retrospect. Affected children may have recurrent respiratory infections. IgG levels usually normalize by 2–3 years. Other classes of immunoglobulins may also be affected. Treatment with IVIG is usually not necessary, but may be considered if symptoms are significant. Children with THI need consistent long-term follow- up care.

Preliminary Results from a Field Study to Investigate the Relationship between Colostrum Quality and Management and Serum Immunoglobulin Concentrations in Dairy Calves

Results of two large national studies indicate that the national preweaning mortality rate in dairy heifers has improved very little over the past ten years (10.8% in National Animal health Monitoring Systems (NAHMS), 1993, 8. 7% in NAHMS, 2002). Failure to reduce mortality in preweaned dairy heifers is partially attributable to poor colostrum management practices. In 1993 (NAHMS), 41 % of 2177 calves sampled between 24 and 48 hrs of age suffered from failure of passive transfer (FPT), or low serum immunoglobulin G (IgG) concentrations. Numerous studies have demonstrated that failure of passive transfer (FPT; calf serum IgG concentration&lt; 10 mg/ml) is associated with a significant increase in risk for morbidity and mortality in the period between birth and weaning (Fowler, 1999; Wells et al, 1996). Conventional factors considered to be important in an effective colostrum management program have included quantity of colostrum fed, quality of colostrum fed (IgG concentration) and quickness (or age at first feeding). Offering a second feeding of colostrum is also frequently recommended. Recently, calf management experts have also begun to evaluate colostrum cleanliness (total bacteria count or total coliform count) as another potentially important factor. Limited studies have suggested that bacteria counts in colostrum not only serve as a pathogen source, but may also reduce efficiency oflgG absorption in the gut. The objective of the current study was to evaluate the relationship between serum IgG concentrations in dairy calves and the aforementioned colostrum management factors (colostrum quantity, quality, quickness, cleanliness).

Transient hypogammaglobulinemia in a child with multiple infections and dysmorphic features

Transient Hypogammaglobulinemia of Infancy (THI) is an uncommon disease entity in which the exact incidence, definition, etiology and outcome remain to be unknown. Affected individuals may be asymptomatic or may have increased frequency of infections. We are reporting a 5 year old boy with dysmorphic features, double left ureter, supravalvular stenosis, laryngotracheobronchomalacia, seizure disorder and multiple serious bacterial infections. The patient had Pneumococcal meningitis at age 7 months and two episodes of Klebsiella sepsis at age 7 weeks and 8 months. He was born full term via spontaneous vaginal delivery with ABO incompatibility for which he received exchange transfusion. Family history is unremarkable. Significant findings in the physical examination included large anterior fontanelle, hypertelorism, downslanted palpebral fissures, bilateral pre-auricular sinuses and wide-shaped, pointed teeth. Laboratory evaluation showed low serum immunoglobulins. Antibodies to tetanus and diptheria toxoids and hemophilus influenza b were present. Lymphocyte subsets, as well as, lymphocyte proliferative response to PHA, con-A and pokeweed mitogens were within normal limits for age. Serum complement levels and nitroblue tetrazolium test (NBT) were also normal. Delayed type hypersensitivity testing with PPD, candida and tetanus remained negative. Cytogenetic studies failed to detect any chromosomal abnormality. HIV testing was negative. The patient was followed closely in Immunology clinic. He did not develop any subsequent problems except for mild upper respiratory tract infections which were managed symptomatically. At 5 years of age, the patient's panhypogammaglobulinemia resolved.

Retrospective study of 25 young weimaraners with low serum immunoglobulin concentrations and inflammatory disease

Twenty-five weimaraners with recurrent infections or inflammatory disease were investigated; their median age was four months (range two to 36 months), and 11 of them were male and 14 female....

B lymphocytes from individuals with common variable immunodeficiency respond to B lymphocyte stimulator (BLyS protein) in vitro

B lymphocyte stimulator (BLyS protein) is a member of the human TNF family of ligands. BLyS induces B-lymphocyte proliferation and Ig secretion in vitro and in vivo. These qualities suggest that it may be useful as a therapeutic in the treatment of immunodeficiencies characterized by low or absent serum immunoglobulin, such as common variable immunodeficiency (CVID). CVID is characterized by the inability to generate adequate serum Ig despite normal or slightly depressed peripheral B, T, and myeloid cell populations. We tested the ability of BLyS to stimulate B lymphocytes obtained from CVID patients. Among five patients studied, 60% (three of five) produced normal quantities of IgM when cultured in the presence of BLyS. B-cell proliferation among patients was comparable, with 60% (three of five) responding to BLyS stimulation. These results suggest that BLyS induces proliferative and Ig-secretory responses in B lymphocytes isolated from some CVID patients and lend support to its potential use in therapy of this disorder.

Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia

To identify patients at high risk of life-threatening infections, we retrospectively analysed the prevalence of infectious complications in 187 chronic lymphocytic leukaemia patients treated in our institution since 1999 and correlated them with clinical features. A questionnaire with detailed questions regarding infectious complications was mailed to patients and their general practitioners. Major infections (requiring intravenous antibiotics or inpatient treatment) were reported in 37 patients (19.8%) and minor infections (requiring oral antibiotics and outpatient treatment) in 113 patients (60.4%). Univariate analysis identified advanced disease (P = 0.02), gender (P = 0.01), duration of disease (P = 0.007), number of previous chemotherapy regimens (P < 0.001), previous therapy with purine analogues and monoclonal antibodies (P < 0.001; P = 0.019), massive splenomegaly (P = 0.03), low granulocyte count (P < 0.001), low serum immunoglobulin concentration (P = 0.005), low haemoglobin concentration (P < 0.001) and high serum lactate dehydrogenase (LDH) concentration (P < 0.001) as risk factors for major infections. In multivariable logistic regression analysis, only the number of previous chemotherapy regimens (risk ratio [RR] = 1.8; 95% confidence interval [CI] 1.2-8.0) and haemoglobin concentration (RR = 0.6; CI 0.5-0.8) remained significant for major infections. The number of previous chemotherapy regimens was the only independent risk factor for minor (RR = 7.6; CI 2.2-25.7) and varicella-zoster virus infections (RR = 2.1; CI 1.3-3.4). In untreated patients, the only risk factor for major infections was LDH concentration. Patients treated with purine analogues or autologous stem cell transplantation had a higher risk of developing viral infections. In conclusion, disease activity and pretreatment extent have a stronger impact on the risk of severe infectious complications than hypogammaglobulinaemia. Preferably, prophylactic strategies should be evaluated in patients defined by these parameters.

Factors related to the risk of neonatal mortality, birth-weight and serum immunoglobulin concentration in lambs in the UK

Neonatal-lamb mortality represents an economic loss and welfare concern. Two factors often associated with the risk of mortality are birth-weight and serum immunoglobulin concentration. We used data from two studies to investigate risk factors for mortality between 2 and 14 days of age and factors affecting birth-weight and serum immunoglobulin concentration at 48 h of age. Dataset 1 included 1339 lambs born on eight farms during the 1995 spring lambing season; dataset 2 included 3172 lambs on seven farms during the 1991 spring lambing season. To account for some of the potential clustering within the data, multilevel models were used. Most (>75%) of the variation in the risk of mortality was at the lamb level. In dataset 1, factors significantly associated with increased odds of lamb mortality included low birth-weight and low serum immunoglobulin concentration. In dataset 2, significant risk factors for mortality included low birth-weight, ewe body-condition score, being born late in the season (relative to other lambs on the farm) and being born in multiple litters. There was a significant interaction between the effects of litter size and birth-weight. (Serum immunoglobulin concentration was not available for dataset 2.) More than half of the variation in birth-weight was at the ewe level, 27% at the lamb level, and 18% at the farm level (dataset 1). Single birth and being male were associated with increased birth-weight in both datasets. In dataset 2 only, increasing ewe condition score and birth early in the study period were also associated with increased birth-weight. Fifty-six percent of the variation in immunoglobulin concentration was at the lamb level, 36% at the ewe level and only 7% at the farm level. Factors associated with reduced serum immunoglobulin concentration included early or late birth in the lambing season, being born later than 14 days after the first lamb born on the farm, multiple-birth litters and maternal mastitis.

The Systemic Inflammatory Response to Cardiac Surgery

The Systemic Inflammatory Response to Cardiac Surgery

Diagnostic findings in 95 Finnish patients with common variable immunodeficiency.

Common variable immunodeficiency is the most frequent of the primary hypogammaglobulinemias. It is manifested by a wide variety of clinical signs and symptoms. In this retrospective, nationwide survey data were collected on all patients with common variable immunodeficiency who were receiving immunoglobulin replacement therapy in Finland to study the prediagnostic clinical picture, diagnostic delay, and diagnostic findings. Ninety-five patients were identified. The median age of the patients was 33 years. Sixteen of the patients were children. Sinopulmonary infections were the most common prediagnostic signs and symptoms; 66% had suffered from recurrent pneumonia, 60% from recurrent maxillary sinusitis, and 45% from recurrent bronchitis. There was a considerable delay in diagnosis. The mean delay was 8 years. At the time of diagnosis chronic pulmonary complications had already developed in 17% of the patients. The diagnosis was based on low serum immunoglobulin concentrations. This study showed that the awareness of common variable immunodeficiency is low. To improve the recognition of hypogammaglobulinemia, it should be suspected in every patient with recurrent bacterial infections. In addition to a low serum IgG concentration, measurement of specific antibody production is recommended to establish the diagnosis before initiation of a life-long and costly replacement therapy.

Pediatric Clostridium difficile: a phantom menace or clinical reality?

Clostridium difficile is the leading cause of nosocomial gastrointestinal illness in adult patients in hospitals. Even though C. difficile disease in adults has been well studied, research on pediatric C. difficile disease is still in its infancy. For many years it has been believed that C. difficile was a disease that affected only adults and was not a problem for children. This erroneous belief arose from the observation that neonates acquire C. difficile quickly (within 48 hours of birth) but show no intestinal symptoms (1–4). More recent evidence has been documented in case reports of pediatric C. difficile and outbreaks of C. difficile disease in pediatric populations (5– 7). Pediatric C. difficile disease has also been associated with the occurrence of severe complications and high mortality rates (8–10). The cascade of events in the pathogenesis of C. difficile disease is similar in children and adults. Normal intestinal microflora are disrupted by antibiotic exposure, medications, or surgery. If the child is then exposed to C. difficile (or its spores), colonization may occur, with production of toxins A and B. These toxins act on enterocytes, causing an inflammatory response and morphologic changes that lead to diarrhea or colitis. Host factors (age, diet, immune response) play an important role in determining whether C. difficile develops into asymptomatic carriage or active disease. Treatment for pediatric C. difficile disease usually relies on metronidazole or vancomycin, but clinical guidelines have not been defined for the pediatric population (11). As in adults, recurrent C. difficile disease that does not respond to conventional therapy develops in a proportion of children treated with antibiotic therapy.

Passive transfer of colostral immunoglobulin G in neonatal llamas and alpacas.

To evaluate precolostral hypogammaglobulinemia in neonatal llamas and alpacas, to determine when postcolostral peak serum IgG concentrations develop, to determine whether differences in postcolostral serum IgG concentrations between llamas and alpacas exist, and to determine postcolostral half-life of serum IgG in llamas and alpacas. Prospective observational study. 29 llama and 10 alpaca crias. Blood samples were collected prior to suckling and on days 1, 2, and 3 after parturition and analyzed for serum IgG concentration by use of a commercial radial immunodiffusion assay. Additional samples were collected on days 8, 13, and 18 from 8 crias to determine mean half-life of IgG. Llamas and alpacas are born severely hypogammaglobulinemic. Mean serum IgG concentrations for day-1, -2, and -3 samples for llamas were 1,578 mg/dl, 1,579 mg/dl, and 1,401 mg/dl, respectively, and for alpacas were 2,024 mg/dl, 1,806 mg/dl, and 1,669 mg/dl, respectively. Peak serum immunoglobulin concentration developed between days 1 and 2. Mean half-life of IgG for all crias was 15.7 days. Although increased mortality has been linked to failure of passive transfer, it is clearly possible to raise crias that have low serum immunoglobulin concentrations. Llamas and alpacas do not differ significantly with respect to immunoglobulin absorption or IgG concentration in neonates. The optimal sampling time for passive transfer status is between 1 and 2 days.

Inhibition of CD23 processing correlates with inhibition of IL-4-stimulated IgE production in human PBL and hu-PBL-reconstituted SCID mice.

CD23, the low affinity serum immunoglobulin E (IgE) receptor, is upregulated on B cells following interleukin (IL)-4 stimulation and is concomitantly cleaved to generate soluble CD23 (sCD23) fragments with cytokine-like activity. Compounds that selectively inhibit the proteolytic release of CD23 to generate sCD23 were assessed for their ability to inhibit IgE production in order to evaluate the contribution of sCD23 in the production of human IgE as well as the ability of such compounds to block IgE production. IgE production was measured in IL-4-stimulated human peripheral blood lymphocytes (PBL) and PBL-reconstituted SCID mice in the presence of a broad-spectrum matrix metalloprotease (MMP) inhibitor, a compound selective for inhibition of CD23 processing over MMPs and an anti-CD23 mAb, MHM6. The two compounds were equipotent in inhibiting IgE production without inhibition of IgG production by IL-4/anti-CD40-stimulated PBL. Soluble CD23 release was also shown to precede IgE accumulation in the cell-free medium. Addition of compound at later times other than day 0 in the 14 day assay resulted in progressively less inhibition of both IgE and sCD23, and exactly paralleled the effect of an anti-CD23 mAb, MHM6 on IgE levels. Both compounds also inhibited the release of CD23 from human RPMI 8866 cells adoptively transferred i. p. to mice. Doses required for inhibition of CD23 correlated well with the doses required for inhibition of IgE production in IL-4-challenged hu-PBL-SCID mice. IgE was selectively inhibited over total IgG in the SCID mice as well. Inhibition of CD23 processing alone is sufficient to inhibit IL-4-stimulated IgE production both in vitro and in vivo.

Serological and virological characterization of clinically diagnosed cases of measles in suburban Khartoum.

Measles continues to be a major childhood disease in terms of global morbidity and mortality. In the main areas of its endemicity the only available means of diagnosis are based on clinical criteria: the presence of a maculopapular rash and fever accompanied by cough, coryza, and/or conjunctivitis. We have studied 38 clinically diagnosed cases of measles in Khartoum, Sudan, by means of serology, reverse transcriptase PCR (RT-PCR) on throat swabs and virus isolation from lymphocytes. On the basis of serology, 28 patients were diagnosed as having an acute measles virus (MV) infection, while in 10 cases the clinical symptoms proved to have other causes. It was shown that in cases with low serum immunoglobulin M (IgM) levels, an additional measurement of IgG or virus-neutralizing antibodies was necessary to discriminate between patients with an acute MV infection sampled during an early stage of the disease and patients who had experienced an MV infection in the more distant past. The serological laboratory diagnosis was validated by an MV-specific RT-PCR: for all confirmed measles cases tested a fragment of the correct size which hybridized with a third MV-specific primer could be amplified, while all serologically negative cases were also RT-PCR negative. MV could be isolated from 17 out of 23 of the serologically confirmed cases, demonstrating that virus isolation is less reliable as a diagnostic tool than serology or RT-PCR. This study stresses the urgent need for a rapid diagnostic field test for measles.

Serum antibody levels and avidities to Escherichia coli O antigens and poliovirus type 1 antigen are increased in children treated for malignant disease.

Treatment of malignant disease in children is often associated with low serum immunoglobulin and reduced specific antibody levels. The aim of this study was to investigate if the functional affinity of specific antibodies in serum and saliva is reduced as well and to evaluate if antigenic exposure or treatment duration affects this antibody avidity. Serum samples were obtained from 45 children and salivary specimens from 30 children with malignant disease. The children were tested either prior to, during, or after chemotherapy. Levels of antibody to E. coli O and to poliovirus type 1 antigens were determined using an ELISA and isotype-specific relative antibody avidity was measured using thiocyanate to elute antibodies from solid-phase immobilized antigens. Children with malignant disease had higher levels and relative avidity indexes of serum antibodies to both antigens as compared to controls. The duration of treatment and type of malignant disease were unrelated to these parameters. In saliva, the level of antibodies to E. coli O antigens, but not to poliovirus type 1 antigen, increased during treatment. Both the amount and avidity of serum antibodies to these antigens are increased in children with malignant disease. This may be due to a dysregulation of the immune system caused by the malignancy and seems not to be dependent on exposure. In contrast, the avidity and levels of these antibodies in saliva seem to correlate with the presence of antigenic exposure.