Serotype-specific serum IgG antibodies to lipopolysaccharides of Pseudomonas aeruginosa in cystic fibrosis: correlation to disease, subclass distribution, and experimental protective capacity

Various studies have demonstrated pronounced systemic IgG response to Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF). However, antibody response to serotype-specific lipopolysaccharides (LPS) has never been studied. ELISA for detection of IgG antibodies to LPS of nine PA-serotypes and to toxin A were performed with serum of 78 CF patients. Anti-LPS profiles of antibodies were confirmed by SDS-PAGE and immunoblotting techniques. The most frequent PA-serotypes found were immunotypes (IT) IT-1 and IT-2, and Habs-3 and Habs-4. Ten patients without PA colonization showed no detectable antibody titers. In patients with chronic PA colonization (n = 46), these antibody titers were significantly (p less than 0.005) higher than in patients with intermittent PA colonization (n = 22). Mean serum antibody titers to LPS of PA IT-1, IT-2, Habs-3, and Habs-4 correlated with duration of PA colonization and with disease severity. Subclass analysis of anti-LPS antibodies revealed elevated levels for all four IgG subclasses and for IgA1. The IgG antibodies to LPS of PA proved to be protective in a murine burn wound sepsis model. We conclude that anti-LPS antibodies to specific PA serotypes in serum may be a sensitive measure of severity and prognosis of CF. Patients with CF show adequate functional immune response to LPS of PA, and it is possible that vaccination against PA before colonization could induce protective immunity.     

Altered antibody isotype in cystic fibrosis: impaired natural antibody response to polysaccharide antigens

Patients with cystic fibrosis (CF) have impaired natural (preinfection) IgG2 antibody responses to Pseudomonas aeruginosa lipopolysaccharide. To investigate the basis for this defect, we measured natural IgG and IgG1-4 antibody levels to Haemophilus influenzae type b polyribophosphate (PRP) and tetanus toxoid by enzyme-linked immunosorbent assay in 24 adult CF patients and 20 normal controls. Immunoglobulin heavy- and light-chain allotypes were determined on 146 Caucasian CF patients and 96 controls. The tetanus toxoid-specific IgG response was predominantly IgG1. CF and control subjects had similar IgG and IgG1 antibody levels. The PRP-specific IgG response was predominantly IgG2. In contrast to tetanus toxoid results, CF patients had lower geometric mean level of PRP-specific IgG compared to normal controls (p = 0.0036). ELISA results were confirmed by liquid-phase 3H-PRP-binding assay: CF patients had a geometric mean serum antibody level of 395 versus 922 ng/ml in controls (p = 0.0044). PRP-specific IgG2 levels were also depressed in CF patients (p = 0.03). CF patients had a lower prevalence of the A2m(2) allotype than the local racially matched control sample (p less than 0.025). Other allotype prevalences including G2m(n) and Km(1) were similar. Impaired IgG2 antibody responses to microbial polysaccharide surface antigens in CF patients might predispose them to persistent endobronchial infection and lead to production of nonopsonizing isotype responses. The potential role of A2m(2), coded for in the H chain locus on chromosome 14, is unknown, but could be related to mucosal IgA2 antibody responses.     

Increased IgG2 and IgG3 concentration is associated with advanced Pseudomonas aeruginosa infection and poor pulmonary function in cystic fibrosis

The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age-matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty-two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV1; p = 0.0001, and p = 0.001 respectively) and high levels of antipseudomonas precipitins (p = 0.008, and p = 0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.     

Increased IgG2 and IgG3 Concentration Is Associated with Advanced Pseudomonas Aeruginosa Infection and Poor Pulmonary Function in Cystic Fibrosis

ABSTRACT. The concentrations of IgG subclass immunoglobulins were determined by radial immunodiffusion in serum from 126 patients with cystic fibrosis (CF). The results were compared to values from age-matched healthy children and adults and correlated to patients age, duration of chronic Pseudomonas aeruginosa infection and lung function parameters. Fifty-two percent of the patients had an elevated concentration of at least one of the IgG subclasses; IgG1 28%, IgG2 16%, IgG3 18% and IgG4 48%. There was significant correlation between elevated serum levels of IgG2, and to a lesser extent IgG3, with decreased lung function (for FEV₁; p =0.0001, and p =0.001 respectively) and high levels of antipseudomonas precipitins ( p =0.008, and p =0.002). A similar correlation was not found for IgG1 and IgG4. IgG subclasses vary in their ability to promote phagocytosis and to activate complement and it is possible that individual differences in the IgG subclass pattern could explain the variable course of this disease.     

IgG subclass deficiency in children with IgA deficiency presenting with recurrent or severe respiratory infections

A group of 22 children presenting with recurrent or severe respiratory tract infections who had low IgA levels (more than 2 SD below the mean for age) were examined for IgG subclass deficiency. Patients were screened for possible defects in neutrophil chemotaxis, bactericidal, fungicidal, and quantitative iodination activity, as well as for complement function. The majority of the patients showed IgG subclass levels below the mean for age. Nine of the children showed definite IgG subclass deficiency and at least two showed definite deficiency of more than one IgG subclass. The predominant subclass deficiency was found to be IgG1. While nine children showed IgG4 levels below the level detectable by the technique used, it is not possible to assess whether these patients are deficient in this isotype since some healthy subjects also give values below the level of detection. Most of the patients who had very low (1-6 mg/dl) or undetectable (less than 1 mg/dl) levels of serum IgA did not show IgG subclass deficiencies, while IgG subclass deficiencies were common among those with borderline low IgA levels (slightly more than 2 SD below the mean for age). Nine children showed total IgG levels close to 2 SD below mean for age, and at least six of these showed IgG subclass deficiency. The result suggests that patients with recurrent and/or severe respiratory infections who have borderline IgA and IgG levels may have IgG subclass deficiencies and if they do could benefit from immunoglobulin therapy.     

Correlation of serum opsonic activity in cystic fibrosis with colonization and disease state: measurement of opsonins to Pseudomonas aeruginosa by neutrophil superoxide anion generation

Serum from patients with cystic fibrosis and normal controls was used to opsonize mucoid and nonmucoid Pseudomonas aeruginosa particles. Opsonic activity was then determined by measuring the production of superoxide anion (O2-) from normal neutrophils stimulated with the opsonized particles. Without any opsonization, mucoid P. aeruginosa stimulated significantly more O2- than nonmucoid P. aeruginosa. Responses to nonmucoid P. aeruginosa observed with heat-inactivated serum from patients with cystic fibrosis were significantly higher (p = 0.008) than those observed with heat-inactivated control sera. Comparisons made between patients who were colonized with P. aeruginosa and those who were not showed that heat activated serum from colonized patients had significantly higher levels of opsonic activity than heat inactivated serum from patients who were not colonized. These differences were observed with either mucoid or nonmucoid P. aeruginosa. A negative correlation was also observed between opsonic activity and clinical status measured by Schwachman scores of colonized patients. These data indicate that in patients colonized with P. aeruginosa the deterioration of their clinical status correlated with increased opsonic activity reflected in the oxidative burst response of neutrophils.     

Serum mucin-associated antigen levels of cystic fibrosis patients are related to their ages and clinical statuses

Mucin levels are generally elevated in sera from many cystic fibrosis (CF) patients as measured by radioimmunoassay using monoclonal antibody 19-9, which is directed against the mucin-associated sialyl Lea antigen. Antibody 19-9 can only be used to measure mucin-associated antigen levels in those patients who are genetically able to make detectable levels of mucin-associated sialyl Lea epitope. Serial studies of 20 patients followed over 3-5 y showed that their serum mucin-associated antigen levels varied directly with respect to the severity of their disease and inversely with their Shwachman-Kulczycki clinical scores (p less than 0.001) and Brasfield chest roentgenographic scores (p less than 0.02). Serum mucin-associated antigen levels in samples from 89 CF patients were generally higher in the older patients (p less than 0.025). Serum mucin-associated antigen levels of CF patients who were colonized with Pseudomonas aeruginosa did not significantly differ from those of uninfected CF patients. The mean serum mucin-associated antigen level of CF patients colonized with Pseudomonas was higher than the mean mucin level of six non-CF bronchiectatic patients whose lungs were colonized with Pseudomonas (p = 0.053). Serum mucin-associated antigen levels are thus related to CF patients' ages and clinical statuses.     

Increased production of serum IgA-class antibody to lipid A in Kawasaki disease

BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). METHODS: We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. RESULTS: The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. CONCLUSION: These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD.     

Deficiency of IgG4 in children: association of isolated IgG4 deficiency with recurrent respiratory tract infection.

To study the relationship between serum IgG subclass deficiency and clinical host defense impairment, we reviewed the clinical and immunologic features of 123 patients with a history of recurrent infection who had been examined for immunodeficiency in our laboratory (group 1). We then compared immunoglobulin isotype levels with those in sera from 127 age-matched control subjects without recurrent infection from whom blood had been drawn for evaluation of atopy (group 2). There was a significantly higher prevalence of IgG4 deficiencies among patients with recurrent infections (17% vs 7%; p less than 0.02), solely because of a higher prevalence of isolated IgG4 deficiency (n = 9; 7.3%) than in atopic control subjects (n = 1; 0.8%; p less than 0.05); there was a comparable prevalence of multiple isotype deficiencies that included low levels of IgG4 (9.8% and 6.3%, respectively). All nine group 1 patients with isolated IgG4 deficiency had severe recurrent respiratory tract infections requiring multiple hospitalizations; in addition, five were atopic, five had asthma, and one had chronic diahrrea. Antibody responses to bacterial polysaccharide antigens were normal for age in all patients with isolated IgG4 deficiency; two had defective antibody responses to protein antigens. Isolated IgG4 deficiency appears to be associated with impaired respiratory tract defenses and may occur in the absence of an easily definable antibody deficiency state. This association suggests a physiologic defense role for mucosal IgG4.     

Clinico-immunologic aspects of IgG subclass deficiency

Serum IgG contains 4 subclasses, IgG1 (60-66%), IgG2 (20-30%), IgG3 (less than or equal to 5%) and IgG4. Individual subclasses vary with respect to their physicochemical and biological properties. IgG subclass concentrations in serum are age dependent. IgG1 and IgG3 reach near to adult levels around the age of 3, IgG2 and IgG4 after the age of 6. Antibodies of certain specificities generally belong to a certain isotype (subclass) due to the isotype restriction. Patients with subclass deficiencies often suffer from recurrent infections. Those with IgG2 deficiency (often occurring with IgA and IgG4 deficiency) develop recurrent infection of the upper and lower respiratory tract often caused by pyogenic microorganisms (Haemophilus, Pneumococcus). Since early initiation of IVIG substitution therapy has a beneficial effect on long term prognosis the importance of early diagnosis is apparent.     

Clinico-immunologic aspects of IgG subclass deficiency

Serum IgG contains 4 subclasses, IgG1 (60-66%), IgG2 (20-30%), IgG3 (less than or equal to 5%) and IgG4. Individual subclasses vary with respect to their physicochemical and biological properties. IgG subclass concentrations in serum are age dependent. IgG1 and IgG3 reach near to adult levels around the age of 3, IgG2 and IgG4 after the age of 6. Antibodies of certain specificities generally belong to a certain isotype (subclass) due to the isotype restriction. Patients with subclass deficiencies often suffer from recurrent infections. Those with IgG2 deficiency coften occurring with IgA and IgG4 deficiency) develop recurrent infection of the upper and lower respiratory tract often caused by pyogenic microorganisms (Haemophilus, Pneumo-(occus). Since early initiation of IVIG substitution therapy has a beneficial effect on long term prognosis the importance of early diagnosis is apparent.     

Role of immunoglobulin subclasses and specific antibody determinations in the evaluation of recurrent infection in children.

We studied humoral immune function in 267 children with recurrent respiratory infections referred to our immunology clinic to determine the most appropriate immunologic studies for evaluating recurrent infections in children. Of this highly selected population, 58% had a partial deficiency in one or more of the major immunoglobulin isotypes or IgG subclasses (defined as at least 2 SD below the normal age-adjusted mean). In none of the patients was there a total absence of an immunoglobulin isotype. The most common abnormality was partial IgA deficiency, which was found in one third of the patients. Twenty-six patients had only partial IgG subclass deficiencies, of which 20 were deficiencies of a single subclass. IgG1 was an isolated partial defect in three patients, IgG3 in five patients, and IgG2 and IgG4 were selective partial defects in six patients each. Tetanus toxoid and pneumopolysaccharide type 3 were the most immunogenic of the immunogens tested; hyporesponsiveness to pneumococcal polysaccharide types 7, 9, and 14 was common. Nineteen percent of the patients with normal immunoglobulin concentrations who were tested had lower-than-expected antibody titers; 42% of those tested with partial isotype deficiencies had deficient antibody responses. Of 25 patients with selective partial IgG subclass deficiencies or combined IgG subclass deficiencies, eight had antibody deficiencies. Our findings indicate that a high proportion of children referred to immunology clinics for recurrent infection have a demonstrable immunologic abnormality. Selective IgG subclass deficiency or a combined IgG subclass deficiency without an associated deficiency in a major immunoglobulin isotype is unusual. Identification of such patients is not predictive of the capacity to form antibodies to the antigens tested in this study and, in our opinion, adds little to the initial evaluation of immune function in such children.     

Pulmonary evolution of cystic fibrosis patients colonized by Pseudomonas aeruginosa and/or Burkholderia cepacia

We analysed the pulmonary evolution (radiological scores and pulmonary function) of 81 cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa (PA), by Burkholderia cepacia (BC) or by both these bacteria, compared to a control group. Pulmonary function was compared in the age bracket 6–13 years. Functional vital capacity (FVC) and forced expiratory volume (FEV₁) values for PA colonized patients were significantly worse than for the control group but better than for children colonized by both organisms. In this last group, the evolution of radiological scores and pulmonary function showed a greater decline 2 years after the first colonization compared to the other groups. FVC and FEV₁ values in patients colonized by BC were not worse than these of patients colonized by PA. Moreover, BC affected older patients with advanced lung disease and often previously colonized with PA. These results suggested that co-colonization by PA and BC could be a more deleterious factor on the pulmonary evolution than the isolated colonization by PA or BC, and that BC could be a severity marker rather than a cause. In addition, after starting the utilization of mouthpieces with filter at single use for spirometry in 1993 (without any other change in preventive measures already taken during hospitalization), incidence of BC decreased from 8.2% to zero, and no new case of BC colonization has been observed over the last 4 years. Conclusion Co-colonization of CF patients by PA and BC is more deleterious for pulmonary evolution than colonization by one of these bacteria alone. Re-inforcement of environmental measures during hospitalization (e.g. use of disposable mouthpieces for spirometry) was sufficient to reduce the transmission of BC. Received: 4 February 1997 and in revised form: 16 September 1997 / Accepted: 23 September 1997     

Longitudinal development of specific and functional antibody in very low birth weight premature infants

We evaluated the formation of specific and functional antibody in preterm infants born weighing less than 1500 g (mean 1088 g) and less than 32 wk gestational age (mean 28.8 wk). Plasma IgG antibody against tetanus and diphtheria toxoids were measured by an enzyme-linked immunosorbent assay. Opsonic activity of heat-inactivated plasma was measured using radiolabeled bacteria, adult polymorphonuclear leukocytes and exogenous human complement. In the presence of complement, the strain of coagulase negative staphylococcus used was opsonized by IgG antibody, and the strain of Escherichia coli by IgM. Geometric mean plasma levels of tetanus and diphtheria IgG antibody fell from birth to 4 months chronological age, but rose significantly by 9 months (approximately 2 months after the third dose of diphtheria, tetanus, pertussis vaccine). However, at 9 months they remained lower than the respective geometric mean levels in 9-month-old term infants (tetanus: p less than 0.001; diphtheria: p = 0.02). The preterm infants' mean plasma IgG staphylococcal opsonic activity fell from birth to 2.5 months, but by 9 months was comparable to that of term infants of the same age. Mean IgM opsonic activity for E. coli was very low at birth in both preterm and term infants. It rose with chronological age, correlating with the rise in total IgM (r = 0.48, p less than 0.001) and by 9 months the mean preterm and term infants' levels of IgM opsonic activity for E. coli were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Demonstration of opsonic and protective activity of human cord sera against type III group B streptococcus that are independent of type-specific antibody

In an effort to further understand the host defense against group B streptococcus (GBS), we examined 71 human cord sera for their content of type III GBS IgG antibody by enzyme-linked immunosorbent assay and correlated the results with opsonic and protective activity against type III GBS. Most cord sera (67%) containing greater than 0.1 microgram/ml of type III GBS IgG antibody promoted phagocytosis and killing in vitro and protection against type III GBS in neonatal rats. However, 26% of cord sera containing less than 0.1 microgram/ml of type III IgG antibody exhibited similar activity in vitro and in vivo against type III GBS. This opsonic and protective activity was retained in IgG fraction of whole serum, and was not directly associated with complement activity or with fibronectin. Further studies are needed to understand the mechanisms responsible for the opsonic and protective activity of some cord sera against type III GBS that may be independent of antibody to the type-specific polysaccharide antigen.     

Deficiencies in opsonic defense to pneumococci in the human newborn despite adequate levels of complement and specific IgG antibodies

We studied the major determinants of opsonophagocytosis against Streptococcus pneumoniae serotypes 14 and 19 in paired cord/maternal sera from 27 healthy term and 24 preterm infants in an attempt to gain more insight in the susceptibility of newborns to pneumococcal infection. For both pneumococcal serotypes studied, opsonic activity in neonatal sera varied greatly, but was moderately to profoundly deficient when compared to paired maternal sera, both in preterm (34.5 and 34.9% of the activity in maternal serum, for serotypes 14 and 19, respectively, p less than 0.001 for both) and in term serum (43.5 and 52.7% of the activity in maternal serum, for serotypes 14 and 19, respectively, p less than 0.001 for both). The opsonic deficiency in preterm sera could be ascribed to a diminished level of the major opsonins for pneumococci, i.e. complement factor C3 deposited on the bacterial surface (69.5 and 66.2% of C3 deposition in maternal serum on serotypes 14 and 19, respectively, p less than 0.01 for both) and specific anticapsular IgG antibodies (48.5 and 14.1% of maternal levels for serotypes 14 and 19, respectively, p less than 0.001 for both). However, the opsonic defect in serum from term infants could not be explained in a similar way, because C3 deposition and specific anticapsular IgG levels were equal to the values found in the paired maternal sera. Therefore, we conclude that the opsonic defect in newborn serum for pneumococci cannot be solely explained by a deficiency in the major opsonins for these bacteria. A dysfunction in these opsonins seems to be a more likely explanation for the observed opsonic defect in the neonate.     

Biliary lipid composition in patients with cystic fibrosis

Lipid composition of gallbladder bile was determined in 20 patients with cystic fibrosis (CF) (9 females and 11 males, ranging in age from 3 to 18 years). The results were compared with 47 normal subjects matched for age, sex, and pubertal stage. In patients with CF, bile was undersaturated with cholesterol before puberty in both sexes and no differences with normal controls could be observed. After puberty, a similar increase in cholesterol saturation was noted in females with CF (85 +/- 15% vs. 130 +/- 38%, p less than 0.01) and normal controls (82 +/- 11% vs. 138 +/- 31%, p less than 0.01). No change in cholesterol saturation could be observed in male patients and controls after puberty. Molar percentage of chenodeoxycholic acid (CDCA) was lower (p less than 0.05) in postpubertal females (31 +/- 9%) and males (36 +/- 7%) with CF compared to controls (42 +/- 8% and 40 +/- 5%, respectively), while cholic acid (CA) was higher in all patients with CF. In females with CF, lithocholic acid (LCA) increased after puberty (2.2 +/- 0.8% vs. 5.3 +/- 2.6%, p less than 0.05) and was higher compared to controls (2.2 +/- 0.8%, p less than 0.001). An increase was also noted for deoxycholic acid (DCA) in postpubertal females with CF (1.7 +/- 2.6% vs. 10.8 +/- 7%, p less than 0.05), but it was lower in both sexes after puberty than in respective controls. The present results suggest that cholesterol saturation of bile in patients with CF is not different from respective controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunofluorescence Studies of Lung Tissue in Cystic Fibrosis

Previous studies have suggested that immune mechanisms contribute to lung injury in cystic fibrosis (CF); however, there have been no comprehensive studies of immunofluorescent staining patterns in CF lung tissue. We performed immunofluorescence (IF) studies for immunoglobulins, C3, and fibrinogen on autopsy frozen lung tissue from 21 CF patients. Results were compared with lung findings in patients without CF. In CF-derived lung tissue fibrinogen was ubiquitous along the alveolar wall, alveolar space, and interstitium. Free immunoglobulin G (IgG) and IgA coated the alveolar surface segmentally in 14 and 6 cases, respectively. Unequivocal interstitial deposits were infrequent and IgM was present in blood vessels in one patient only. Intra-alveolar and interstitial inflammatory cells demonstrated cytoplasmic IgG, IgA, and IgM, respectively, in 18, 14, and 6 patients. C3 was seen only segmentally along the alveolar wall in two patients and in blood vessels in one. Antinuclear antibody (ANA) staining of interstitial cells for C3 and immunoglobulins was seen in five patients, four of whom had interstitial pneumonitis. Insignificant amounts of alveolar or interstitial fibrinogen and immunoglobulins in inflammatory cells were seen in controls in the absence of lung inflammation. The IF patterns were similar in the inflammatory lesions of CF and control specimens.

The IF patterns observed in CF lung tissue are consistent with nonspecific vascular leakage and chronic inflammation with little evidence of immune complex deposition in the interstitium or blood vessels. This study confirms previous reports of ANA activity in CF patients, although the significance of this finding is unknown.     

IgG subclass deficiency in children with congenital heart disease

This study of 66 children with congenital heart disease found 26 (39%) with IgG subclass deficiency, the majority being of the IgG₄ isotype. Conventional immunoiogical assessment (IgG, IgA, IgM, T cell) revealed 21 (32%) with immunodeficiency, while inclusion of IgG subclass assessment revealed a total of 35 (53%) of the 66 children had immuno-deficiency. Children with conotruncal lesions appeared to be predisposed to immunodeficiency affecting T cells and IgG subclasses (especially IgG₄) while those with shunt and stenotic lesions had a broad spectrum of immunoglobulin deficiencies. There was significant correlation between immunodeficiency and proneness to infection in these children (p < 0.01). These results suggest that immunodeficiency is a frequent occurrence in children with congenital heart disease, and that IgG subclass measurements should be added to the diagnostic work-up.     

Opsonic Activity,Phagocytosis, and Bactericidal Capacity of Polymorphs in Undernutrition

Fifteen undernourished infants and children were studied for opsonic activity of plasma, and for phagocytosis and intracellular bactericidal capacity of polymorphonuclear leucocytes. The opsonic activity was slightly increased and there was a significant decrease in bacterial killing by polymorphs of malnourished individuals compared with healthy controls. Phagocytosis was comparable in the 2 groups. In 3 patients, the impairment of bacterial killing was reversed to normal on recovery from nutritional deficit. It is suggested that this may be one possible mechanism of infection-nutrition interaction.