IgA antibodies to Klebsiella pneumoniae in ankylosing spondylitis

Serum IgA antibodies to Klebsiella pneumoniae were measured in 65 patients with ankylosing spondylitis (AS) during different phases of disease activity and compared with the antibody level in 21 psoriatic arthritis (PsA) patients, 43 rheumatoid arthritis (RA) patients and 57 healthy controls. The mean IgA antibody to Klebsiella in AS patients with an erythrocyte sedimentation rate (ESR) greater than or equal to 15 mm/h was significantly higher than the antibody level in patients with an ESR less than 15 mm/h (p less than 0.02) and tended to increase with rising ESR. There was a significant difference in anti-Klebsiella antibody levels between AS patients with an elevated ESR and antibody levels in PsA patients (p less than 0.001), RA patients (p less than 0.001) and healthy controls (p less than 0.005). There was no difference between healthy controls and patients with PsA, RA or AS patients with a low ESR. The IgA anti-Klebsiella antibody was specifically absorbed out from sera with inactivated klebsiella pneumoniae organisms. Antibody levels to Candida albicans and Escherichia coli did not differ in patients vis-à-vis control subjects. The mean serum anti-Klebsiella IgA level was found to be higher in patients who were either clinically active or had positive faeval cultures, when compared with patients with inactive disease and negative cultures, but these differences were not statistically significant, although when both parameters were examined together a significant additive effect was detected (p less than 0.001). It is concluded that patient with AS exhibit a specific elevation of serum IgA antibody to Klebsiella antigen.     

Bone marrow IgA and IgA subclass synthesis in ankylosing spondylitis.

To investigate the source of increased production causing elevation of serum immunoglobulin A (IgA) in ankylosing spondylitis (AS) we studied the production of IgA and IgA subclasses in cultures of bone marrow cells as well as the relative numbers of IgA and IgA subclass containing bone marrow cells obtained from 24 patients with AS and 22 healthy control individuals. In patients with AS serum levels of IgA, IgA, and IgA2 were significantly higher compared to controls. The IgA1 subclass in patient's serum contributed significantly less to the total IgA compared to controls. In bone marrow cultures of patients with AS and controls the production of IgA, IgA1 and IgA2 were in the same range as were the relative numbers of bone marrow cells containing IgA and IgA subclasses. However, the immunoglobulin synthesis by bone marrow cells of patients with AS showed a significant shift towards IgA1 compared to controls. Our findings indicate that the regulatory abnormalities of IgA production in AS involve both the IgA1 and IgA2 subclass and suggest that an abnormal mucosal immune response could be responsible for chronic overproduction of IgA and the elevation of serum IgA in patients with AS.     

Increased IgA antibodies to cytokeratins in the spondyloarthropathies.

OBJECTIVES--Increased levels of IgA antibodies to cytokeratin-18 (CK-18) and epidermal keratins (EpK) in the sera of patients with rheumatoid arthritis (RA) have been demonstrated previously. In the present study investigations were carried out to determine whether levels of these autoantibodies were also raised in the spondyloarthropathies, and whether there was any association with particular disease manifestations. METHODS--Using specific enzyme linked immunosorbent assays (ELISA) measurements were taken of IgA, IgG and IgM antibodies to EpK and to CK-18 in the sera of patients with psoriatic arthropathy, ankylosing spondylitis (AS), Reiter's syndrome, psoriasis and in normal subjects. RESULTS--IgA antibodies to both EpK and CK-18 were significantly increased in sera from patients with psoriasis and psoriatic arthropathy but not in the sera from the patients with AS or Reiter's syndrome, or in the controls. In psoriatic arthritis, however, these levels were significantly higher only in those patients with peripheral joint disease and not in those with axial arthritis alone. There was no significant increase in antibody levels in patients with AS or Reiter's syndrome. There were no differences in the levels of IgG or IgM antibodies to CK-18 or EpK between the patient groups and controls. CONCLUSIONS--Raised levels of IgA antibodies to CK-18 and EpK in psoriatic arthropathy and psoriasis probably reflect exposure of intracellular cytokeratin antigens to the immune system after damage to cytokeratin containing cells, and suggests a common pathogenic mechanism in these conditions which involves production of cytokeratin autoantibodies. In patients with psoriatic arthropathy, such a mechanism appears only to be operating in patients with peripheral joint involvement and not in those with axial arthritis.     

Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites

Elevated serum levels of IgA, IgA1, and IgA2 rheumatoid factors (RF) were demonstrated by enzyme-linked immunosorbent assay in 69%, 73%, and 36%, respectively, of 100 patients with rheumatoid arthritis (RA), whereas fewer than 5% of 100 healthy donor sera contained elevated levels of these RFs. In serum samples from 125 controls with 4 different chronic diseases (systemic lupus erythematosus, ankylosing spondylitis, bronchial asthma, and polyarteritis nodosa), levels of IgA-, IgA1-, and IgA2-RF were found to be increased in 7%, 7%, and 8%, respectively. Comparison of RF levels in samples of serum, synovial fluid (SF), and saliva from RA patients indicated local production of both IgA-RF subclasses in salivary glands and in synovial tissue. Significant positive correlations were found between levels of IgA-RF subclasses in SF and serum, but not in serum and saliva or in SF and saliva. Fractionation of serum, SF, and saliva from patients with RA (by high performance liquid chromatography under acidic conditions) demonstrated that both IgA subclasses with RF activity occur mainly in fractions that also contain IgM. The results of this study show that 1) IgA-RF in serum and SF is mainly of IgA1 subclass, 2) both IgA-RF subclasses are produced locally in salivary glands and in synovial tissue, 3) the production of both IgA-RF subclasses at mucosal and nonmucosal sites is independent from each other, and 4) both IgA-RF subclasses occur predominantly in polymeric form in serum, SF, and saliva in RA patients.     

Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis

BACKGROUND: Increased levels of collagen types I, III and V are found in strictures of patients with Crohn's disease (CD) compared with normal gut tissue. Type IV collagen is present in the basement membranes, basal lamina, retina and cornea. Elevated levels of antibody to Klebsiella pneumoniae are found in both active CD and active ankylosing spondylitis (AS) patients compared with healthy controls. METHODS: Reactivities for immunoglobulin class-specific antibodies (IgM, IgG and IgA) against collagen types I, III, IV, V and whole K. pneumoniae were measured by ELISA in nine patients with early CD and 10 with late CD from King's College Hospital and 12 late CD patients and 36 HLA-B27-positive AS patients from Middlesex Hospital and was compared with values for 26 healthy controls from the Blood Transfusion Service in London. RESULTS: Levels of class-specific IgM, IgG and IgA antibodies to collagen types I, III, IV, V and K. pneumoniae were significantly elevated in early and late CD patients compared with healthy controls (P<0.001). Levels of IgM, IgG antibody to the four collagen types and K. pneumoniae were also significantly elevated (P<0.001) in AS patients compared with healthy controls. In addition, the level of IgA antibody to K. pneumoniae was elevated in AS patients (P<0.001). Furthermore, a positive correlation between antibody levels to collagen types I, III, IV and K. pneumoniae was demonstrated in both early and late CD patients and in those with AS, whilst a positive correlation to type V was found in early CD. CONCLUSION: The role of K. pneumoniae and anti-collagen antibodies in the aetiopathogenesis of CD and AS requires further study.     

Immunoglobulin A antibody against hepatitis B core antigen of polymeric and monomeric forms, as well as of IgA1 and IgA2 subclasses, in acute and chronic infection with hepatitis B virus

Solid-phase radioimmunoassays using monoclonal antibodies were used to assay antibody to hepatitis B core antigen of immunoglobulin A class in terms of polymeric and monomeric forms, as well as of IgA1 and IgA2 subclasses, in the serum of persons infected with hepatitis B virus. The level of secretory immunoglobulin A antibody was significantly higher in patients with acute hepatitis (mean +/- S.E., sample per normal ratio = 29.2 +/- 1.9) than that in asymptomatic carriers (2.1 +/- 0.1), patients with chronic persistent hepatitis (3.5 +/- 0.5), patients with chronic active hepatitis (6.9 +/- 1.3) or patients with cirrhosis (5.8 +/- 1.1). In acute type B hepatitis, only polymeric immunoglobulin A antibody of either IgA1 or IgA2 subclass was detected. In contrast, in chronic infection, antibody to hepatitis B core antigen of IgA2 subclass was found in the polymeric form, but antibody of IgA1 subclass was detected in both polymeric and monomeric forms.     

Serum IgA subclasses and molecular forms in HIV infection: selective increases in monomer and apparent restriction of the antibody response to IgA1 antibodies mainly directed at env glycoproteins.

In a study population representing different CDC stages of HIV infection, 58% exhibited IgA hypergammaglobulinemia resulting from proportional increases in both the IgA1 and the IgA2 subclasses. These increases were detected early in infection, did not correlate with CD4 count, and remained elevated throughout disease progression. Absolute concentrations of polymeric IgA present within each subclass were unchanged, indicating that increased production of monomeric IgA1 and IgA2 were responsible for elevations of total IgA. These elevations were not completely attributable to a specific antibody response to viral infection, since Western blot analysis of purified IgA samples indicated that HIV-reactive IgA antibodies could be demonstrated only within the IgA1 subclass. Dominating IgA1 anti-HIV responses were also observed in two secretory IgA samples isolated from colostrum of healthy HIV seropositive mothers, suggesting that a similar isotype restriction exists in the mucosal IgA compartment. The binding of IgA1 to HIV proteins contrasted markedly to that observed with identical concentrations of IgG purified from the sera of the same patients. While IgG reacted more intensely and broadly with all HIV proteins, IgA1 antibodies were directed predominantly against envelope glycoproteins. In many patients, a total lack of IgA1 reactivity to gag and pol proteins was accompanied by intact IgG responses to these same antigens. Though all IgA samples examined reacted with HIV, fewer responses to gp160, gp120, and p24 were observed in samples from AIDS and AIDS-related complex (ARC) patients, suggesting a declining titer of IgA antibodies against these antigens may be associated with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical implications of IgA rheumatoid factor subclasses.

OBJECTIVES--To evaluate the diagnostic and pathogenetic significance of IgA rheumatoid factor (RF) subclasses in rheumatoid arthritis (RA). METHODS--Rheumatoid factors of the IgA class and IgA1 and IgA2 subclasses were measured by enzyme linked immunosorbent assay in 58 patients with RA, 31 patients with other rheumatic diseases, 30 non-rheumatic individuals with increased concentrations of IgA RF, and in 100 randomly selected healthy controls. RESULTS--Using a 95% cut off for the controls, 55% of the RA patients had increased total IgA RF, 64% IgA1 RF, and 60% IgA2 RF. RA patients with extraarticular manifestations more often had increased concentrations of IgA RF and both subclasses than patients without such manifestations (p < or = 0.01). Nearly all (31/32) RA patients with increased IgA RF had increases in both IgA RF subclasses, compared with 67% (20/30 of nonrheumatic symptom free individuals with increased IgA RF (p = 0.002). CONCLUSION--Increased concentrations of the IgA2 RF subclass appears to be more specific for RA than increased IgA1 RF. Measurement of IgA RF subclasses may be clinically useful.     

The effect of age and natural priming on the IgG and IgA subclass responses after parenteral influenza vaccination.

This study investigated the effect of natural priming and age on serum IgG and IgA subclass responses after parenteral trivalent influenza vaccination. Sera from 18 young children and 8 adults were collected at various times after vaccination. An ELISA was performed to quantify the concentrations of antibody subclasses. The children were divided into primed and unprimed groups based on the presence of prevaccination serum antibodies. In both children and adults, IgG1 and IgA1 were the predominant IgG and IgA subclasses detected after vaccination. No IgG2 responses were detected in sera of unprimed children, and the proportion of the IgG2 response was lower in primed children than in adults. This suggests that the IgG2 immune response in young children is dependent on previous priming and may mature later than the other IgG subclasses after parenteral influenza vaccination.     

IgA antibody response to klebsiella in ankylosing spondylitis measured by immunoblotting.

IgA antibodies to Klebsiella pneumoniae var oxytoca and Proteus mirabilis were measured in 66 patients with ankylosing spondylitis (AS) and 31 with rheumatoid arthritis (RA) and in 51 healthy control subjects, using an immunoblotting technique. The number of antigenic bands to klebsiella on nitrocellulose membrane was higher in 28 patients with active AS than in 38 patients with inactive AS, 31 patients with RA, and 51 healthy control subjects; comparatively smaller increases were found against proteus. In two patients with AS the synovial fluid and the corresponding serum sample showed an identical antibody pattern. Increases in IgA antibodies to klebsiella in patients with AS confirm previous studies using other techniques.     

Production and Characterization of Murine Monoclonal Antibodies Recognizing Conformational and Linear Epitopes Localized on Human IgA2 Molecules

Background: There are two subclasses of human IgA (IgA1 and IgA2) that differ in antigenic properties and in chemical composition. The constant domains of α1 and α2 heavy chains have >95% sequence homology though major structural differences exist in the hinge region. Quantitation of IgA subclass levels depends on the availability of monoclonal antibodies (MAbs) specific for conserved conformational or linear epitopes restricted to each subclass. Objective: To produce, select and characterize monoclonal antibodies specific for human IgA2. Methods: Splenocytes from BALB/C mice immunized with a human IgA2 myeloma protein were fused with SP2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine and thymidine (HAT) selective medium and cloned by limiting dilution assay. Antibody (Ab) secreting cells were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of secreted MAbs was further analyzed, using a panel of purified myeloma proteins and some animal sera by ELISA and immunoblotting. The affinity constant (Kaff) was also determined by ELISA. Results: Four murine hybridoma clones designated 2F20G5, 2F20B5, 3F20E3 and 6F20H11 were obtained that secreted MAbs specific for the human IgA2. 2F20G5 and 6F20H11 MAbs react with linear epitope(s) while 2F20B5 and 3F20E3 react with conformational epitope(s) located to human IgA2 subclass. 2F20G5 MAb displays a weak cross-reactivity with monkey and rabbit sera and a strong cross-reactivity with cat and dog sera while the other three MAbs showed no cross-reactivity with the animal sera tested. Conclusion: These MAbs, especially 6F20H11 with high affinity constant (6.03 ×109 M-1) are useful tools for quantitation of human IgA2 subclass levels in various diseases. Cross-reactivity of 2F20G5 MAb with some animalsera suggests phylogenic conservation ofthe epitope recognized by this MAb.     

Failure of Klebsiella pneumoniae antibodies to cross-react with peripheral blood mononuclear cells from patients with ankylosing spondylitis

Cross-reactivity between antibodies to 2 strains of Klebsiella pneumoniae (K43 and F77) and the peripheral blood lymphocytes of patients with ankylosing spondylitis (AS) was examined in 3 separate antibody binding and cytotoxicity assays. Using K pneumoniae antisera in a chromium release cytotoxicity assay, we found no difference in the reactions of cells from AS patients and those from control subjects. This result contrasts with the results of previous studies. Similarly, using an enzyme-linked immunosorbent assay, we detected no significant increase in antibody binding to peripheral blood mononuclear cells (PBMC) in HLA-B27 positive patients with AS. Low levels of antibody binding were detected by a fluoresceinated antibody binding assay; however, normal rabbit serum, which was used as a control, was shown to have a binding affinity for PBMC that was significantly greater than that of specific K pneumoniae antisera. The results of our present study do not support the concept of a specific cross-reactivity between antibodies to K pneumoniae and the PBMC of patients with AS who are HLA-B27 positive.     

IgG and IgA subclass distribution of total immunoglobulin and rheumatoid factors in rheumatoid tissue plasma cells

The subclass distribution of IgG and IgA plasma cells, and in IgG and IgA rheumatoid factor (RF) producing cells was studied in sections of synovial tissue from seropositive RA and various types of seronegative arthritis, including ankylosing spondylitis, psoriatic arthritis, and Reiter's syndrome. The study was performed with immunofluorescence technique and monoclonal IgG and IgA subclass specific antibodies. IgG RF producing cells were identified by their ability to bind and activate factors both in the early (C3) and late (C5b-9) part of the complement cascade. IgA RF cells were identified by double staining experiments with heat-aggregated IgG and monoclonal antibodies to IgA subclasses. In 23 tissues tested for total IgG, IgG1 cells were usually predominant, while the frequency of IgG3 cells was usually higher than that of IgG2. In 19 tissues also tested for IgA, both IgA subclasses were present in all tissues. IgA1 plasma cells were always predominant, with a mean ratio of IgA1 to IgA2 cells of approximately 10. In the 13 tissues tested for RF-producing cells, the highest frequency of IgG RF cells was found among the IgG3 cells, followed by IgG1 and IgG2. IgA RF cells were found in only one case, all cells being IgA1.     

Serum IgA to enterobacteria in ankylosing spondylitis

The aetiology of ankylosing spondylitis (AS) may involve certain enterobacteria. It is therefore interesting that serum polymeric IgA, a precursor of secretory IgA, was statistically elevated in active AS (n = 35) and that levels were comparable to those found in yersiniosis (n = 12); this might indicate antigenic stimulation by bacteria which are present in the intestines of AS patients. However, specific serum IgA to the incriminated enterobacteria Klebsiella, Shigella and Yersinia, as determined by ELISA, was not raised in the above AS patients. Nor were these titres raised in patients with idiopathic reactive arthritis (n = 21). In contrast, yersiniosis (n = 12) and shigellosis (n = 96) patients displayed marked increases in specific serum IgA titres to the respective infectants. It is proposed that AS may involve a set of enterobacteria rather than a few suspected species. Thus, despite the lack of raised group averages, screening of individual patients for specific IgA to several indicated bacteria might disclose whether or not raised serum IgA is related to enterobacterial activity. Apart from this, the above supports other reports indicating that serum IgA may be a useful parameter to assist in monitoring of disease activity in AS. Finally, it is suggested that study of a homogeneous group of reactive arthritis patients might facilitate aetiological research of seronegative arthropathies such as AS.     

Distribution of subclasses in a series of 62 sera with IgA paraprotein

IgA1-2 subclass distribution was determined in a series of 62 sera with diagnosed IgA paraprotein. Throughout the series the participation of IgA1 : IgA2 subclasses showed a ratio 9 : 1 even after division of the series into myeloma and nonmyeloma paraproteinemias. On dividing the series according to the antigenic type of the light chains, IgA2 paraproteins with kappa light chains predominated over the lambda type (6 : 1).     

IgA antibodies to gram-negative bacteria in the serum and saliva of patients with ankylosing spondylitis

The concentration of IgA and titre of IgA antibodies to several Gram-negative bacteria were measured in the serum and parotid saliva of patients with AS and normal tissue-typed individuals. Salivary IgA and antibody levels in the patients were identical with the control population. The serum antibody level against Yersinia enterocolica 0:3 was slightly raised in patients but there was no difference in the reactions to Klebsiella oxytoca strain MX100 or Escherichia coli 0111.B4. The serum IgA level was elevated in patients with AS, irrespective of HLA B27. We conclude that this approach is unlikely to provide convincing evidence of a link between Gram-negative bacteria and ankylosing spondylitis.     

Immunogenic and Antigenic Epitopes of Immunoglobulins X: Monoclonal Antibodies Specific for Human IgA, the IgA1 and IgA2 Subclasses and an nA2m(2) Iso-Allotypic Epitope

Monoclonal antibodies (McAb) specific for human IgA, the IgA1 and IgA2 subclasses and the iso-allotypic epitope nA2m(2) have been produced. Three distinct McAb recognize an IgA1-specific epitope expressed in the C alpha 2 domain or the hinge region whilst a further McAb is directed possibly to an IgA1 hinge region epitope. The McAb having nA2m(2) specificity recognizes an iso-allotypic epitope expressed within the Fab region. IgA1 and IgA2 epitopes were detected in gorilla but not rhesus or baboon sera suggesting that the IgA subclasses represent a recent gene duplication even. However, these epitopes were also detected in some non-primate sera.     

Long lasting IgG subclass and antibacterial polysaccharide antibody deficiency after allogeneic bone marrow transplantation

Serum IgG subclasses were measured by a competitive indirect immunoassay with monoclonal antibodies in 31 leukemic patients before and after bone marrow transplantation. Antibodies to Hemophilus influenzae type b (Hib) capsular polysaccharide were determined in 28 cases. Abnormally low or borderline subclass (mostly IgG2 and IgG4) levels were found late after transplant in 23 infected and noninfected patients. These levels persisted for as long as 25 months, in association with low or borderline IgA levels in 78% of the cases. IgG2, IgG4, and IgA often showed a parallel evolution, whereas IgG1, IgG3, and IgM often varied together in the opposite way. Class but not subclass deficiencies were more frequent in patients with graft-v-host disease (GVHD). Subclass abnormalities predominated in infected patients, with mean levels correlating with the severity of infections; however, the abnormalities are not clearly predictive of infections in individual cases. Most patients with Hib pneumonia showed virtually no IgG antibody response to Hib, and one-half of the patients had a moderate IgM and IgA response. In the whole series, many sera collected greater than 1 year after graft contained very low or undetectable antibodies. Correlation between anti-Hib antibody and IgG2 levels was significant but weak because of discrepancies that were only partially explained by the subclass distribution of the antibodies.     

Antibody-enhanced pneumococcal adherence requires IgA1 protease

IgA, the major class of Ig in secretions, classically functions by interfering with microbial attachment to host tissues. Many mucosal pathogens, including Streptococcus pneumoniae, express an IgA1 protease that may circumvent the protective effects of this Ig subclass. Because these proteases are specific for human IgA1, we generated human mAbs to the major surface antigen of the pneumococcus, its capsular polysaccharide, and tested their effect in a colonization model of bacterial adherence to respiratory epithelial cells in culture. Rather than inhibiting adherence, type-specific IgA1 markedly enhanced bacterial attachment to host cells, but only when cleaved by IgA1 protease. Neither antibodies of protease-insensitive subclasses (IgA2 and IgG) nor those directed against heterologous capsules had such activity. The adherence-promoting properties of cleaved antibodies correlated with the cationic characteristics of their variable segments, suggesting that bound Fab fragments may neutralize the inhibitory effect of negatively charged capsules on adhesive interaction with host cells. Coating of pneumococci with anticapsular polysaccharide antibody unmasked the bacterial phosphorylcholine ligand, allowing for increased adherence mediated by binding to the platelet activating factor receptor on epithelial cells. In addition, our findings provide evidence for a novel function of bacterial IgA1 proteases. These enzymes may enable pathogens to subvert the antigen specificity of the humoral immune response to facilitate adhesive interactions and persistence on the mucosal surface.     

IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage.

Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some may suffer from frequent mainly respiratory infections. The aim of our study was to determine the frequency of IgA and/or IgG subclass deficiencies and the rate of chronic pulmonary damage secondary to recurrent pulmonary infections in these children. Serum IgA and IgG subclass levels were measured in 225 children aged 6 months to 6 years with recurrent sinopulmonary infections (44 with recurrent upper respiratory tract infections, 100 with recurrent pulmonary infections and 81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage due to recurrent infections in patients with recurrent pulmonary infections CT scans of thorax were also obtained. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or IgG subclass deficiency was 25% in patients with recurrent upper respiratory tract infections, 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary infection. In IgG subclass deficiencies sequel changes, although not statistically significant, were observed five times more frequently than that of IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%) patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3 deficiency). On the other hand, pulmonary sequels were observed in 12 patients (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We therefore suggest that determination of antibody levels and evaluation of pulmonary alterations is crucial in patients with recurrent sinopulmonary infections since the deficiency of antibodies is associated with a greater pulmonary damage.