A longitudinal study of plasma and salivary antibodies in HIV-1 infection

The patterns of plasma and salivary IgG and IgA antibodies reacting to HIV-1 proteins were followed in seven HIV-1-infected individuals for a period of 18-40 months. Western blot analyses revealed diversities in specificity of these antibodies among subjects; however, for the same subject, the specificity profile remained consistent throughout the entire follow-up period. The staining intensities of plasma IgG from two subjects were associated with plasma viral load. The band intensities of salivary IgG were mostly determined by plasma IgG; the health of the oral cavity might also influence the transudation of salivary IgG antibodies. The binding intensities of plasma and salivary IgA antibodies specific for certain viral proteins were associated with plasma viral load in some subjects as well.     

Cross-clade HIV-1-specific neutralizing IgA in mucosal and systemic compartments of HIV-1-exposed,persistently seronegative subjects

There is an urgent need for a universally effective HIV-1 vaccine, but whether a vaccine will be able to protect against HIV-1 of different clades is a significant concern. IgA from HIV-1-exposed, persistently seronegative (HEPS) subjects has been shown to neutralize HIV-1 and to block epithelial HIV-1 transcytosis, and it may target novel HIV-1 epitopes. We have tested the ability of plasma and mucosal IgA purified from HEPS subjects to neutralize HIV-1 primary isolates of different viral clades and phenotypes. IgA from two groups of HEPS subjects was tested: sex workers from Nairobi, Kenya, where clades A and D predominate, and the heterosexual partners of individuals infected by clade B virus. HIV-1-infected and low-risk uninfected individuals were included as controls. IgA purified from the blood, genital tract, and saliva of most HEPS sex workers demonstrated significant cross-clade HIV-1 neutralization, whereas a more clade-restricted pattern of neutralization was found in partners of clade B-infected individuals. IgA purified from HIV-1-infected individuals also mediated cross-clade neutralization, whereas IgA from uninfected controls lacked neutralizing activity. In conclusion, mucosal and plasma IgA from HEPS subjects neutralizes HIV-1 of different clades. This ability to induce HIV-1-specific systemic and mucosal IgA may be an important feature of an effective prophylactic HIV-1 vaccine.     

Immunoglobulin levels in saliva in individuals with selective IgA deficiency: Compensatory IgM secretion and its correlation with HLA and susceptibility to infections

Total levels of IgA, IgM, and IgG were measured in unstimulated whole saliva and serum from 63 individuals with selective IgA deficiency. Values were compared with the incidence of upper respiratory tract infections, antibiotic treatments (necessitated by upper respiratory tract infections), and HLA antigens. A statistically significant increase in salivary IgM and IgG levels was noted in individuals with selective IgA deficiency compared to healthy normal individuals. Healthy individuals with selective IgA deficiency did not have increased concentrations of salivary IgM compared to infectious-prone patients. Nor was there any correlation found between proneness to infections and HLA antigens or between salivary IgM or IgG levels and HLA antigens in this patient material.     

Salivary and serum antibodies in patients with Yersinia enterocolitica infection

The systemic and secretory antibody response in patients with yersiniosis was studied by measuring Yersinia antibodies of various isotypes (IgG, IgA and IgM) and the total concentrations of the corresponding Ig classes in serum and saliva. Specific antibody activities of IgG (IgG antibody concentration divided by IgG concentration) were almost identical in serum and saliva of all patients although the pair of values varied from patient to patient. Almost all salivary IgG of these patients was therefore probably a transudate from the blood. Specific antibody activities of IgA and of IgM, on the other hand, varied independently in serum and saliva. Occasional great differences between serum and saliva values indicate that most of the salivary IgA and IgM (more than 90%) is produced locally at least in some individuals. The local anti-Yersinia response was restricted to IgA in some individuals, to IgM in others, whilst yet other patients produced salivary antibodies of both isotypes.     

Salivary human immunodeficiency virus (HIV)-1-specific immunoglobulin A in HIV-1-exposed infants in Kenya

Humoral immunity, and specifically immunoglobulin A (IgA) that is directed against human immunodeficiency virus (HIV)-1, may contribute to protection against HIV-1 acquisition at mucosal surfaces. HIV-1-specific IgA has been detected in genital tract secretions of HIV-1-uninfected commercial sex workers with HIV-1 exposure, and may be produced in parotid saliva by infants exposed orally to HIV-1 during delivery and breastfeeding. To explore this hypothesis, we collected saliva from 145 infants aged < or = 6 months enrolled in a perinatal HIV-1 transmission study in Nairobi and from 55 control infants without HIV-1 exposure who were born to HIV-1-seronegative mothers. Among the 145 infants, 115 (79%) remained uninfected during the 12-month study period and 30 (21%) became HIV-1-infected during follow-up. Nine (8%) of the 115 HIV-1-exposed, uninfected infants had detectable levels of HIV-1 gp160-specific IgA compared with four (13%) of 30 infected infants and none of 55 control infants (P = 0.47 and P = 0.03 respectively). Among the nine HIV-1-exposed, uninfected infants with positive assays, median age was 1 month and none acquired HIV-1 during follow-up. We conclude that HIV-1-specific salivary IgA responses may be generated by very young infants exposed perinatally to maternal HIV-1. Mucosal responses would be an appropriate target for paediatric vaccines against breast milk HIV-1 transmission.     

Induction of Salivary Antibody Responses in Rats after Immunization in Peyer''s Patches

We examined salivary, milk, and serum antibody levels after immunization in the Peyer's patches (Pp) of rats with horse spleen ferritin. Priming of the Pp one day after parturition led to the appearance of IgG, but not IgA or IgM, anti-ferritin antibodies in saliva 9 days later. IgG and IgM antibodies were detected both in milk and in serum, whereas IgA antibodies could only be demonstrated in milk. During a second lactation period the salivary antibodies had vanished but IgG antibodies could still be detected in milk and serum. During a third lactation period, when the rats were immunized in the Pp a second time, not only IgG but also IgA anti-ferritin antibodies appeared in the saliva. Salivary IgG antibody levels and milk IgG, IgM, and IgA antibody levels were higher than those observed after primary immunization in the Pp. The IgG antibody activity in the saliva was positively correlated to the serum IgG antibody activity. It is concluded that salivary IgA antibody responses can be induced by immunization in the Pp. The results of this study suggests that IgA antibodies detected in saliva are produced locally by cells that have migrated from the intestinal lymphoid tissue to the salivary glands.     

Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine. The National Institute of Allergy and Infectious Diseases-sponsored AIDS Vaccine Evaluation Group.

Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum. When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had received rgp160 on a month 0, 1, 2, and 5 schedule, five had received alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus vaccine. Five volunteers consented to the donation of parotid saliva but not genital secretions. Prior to immunization, parotid saliva specimens were available for 11 of 22 volunteers, seminal plasma (SP) specimens were available for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for 5 of 22 volunteers, and serum was available for 22 of 22 volunteers. These baseline specimens and specimens collected at 1 and 7 months after the final immunizations were assessed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1 MN rgp160. No augmentation in HIV rgp160-specific IgG or IgA antibody production in either parotid saliva or serum specimens of vaccinees compared to that in controls was observed after immunization. There were insufficient numbers of SP or CVL specimens available for statistical comparisons between vaccinees and controls. Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11 volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum specimens. Fewer volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of 5 CVL samples, and 12 of 22 sera.     

Salivary sIgA response in HIV-1 infection.

Local and systemic production of total and HIV-1 specific IgA was determined in whole saliva and serum from 45 HIV-1-infected individuals and 15 healthy controls. The antigenic domains important for sIgA and IgG binding, respectively, was investigated with epitope mapping using synthetic peptides of HIV-1 proteins. Decreased levels of total sIgA in saliva were found among patients with low CD4+ cell counts in advanced stages of acquired immunodeficiency. HIV-1 specific IgA response, predominantly directed to the envelope proteins, was found in saliva and serum also at later stages of disease. Analyses using peptide enzyme-linked immunosorbent assays (ELISA) showed that the sIgA antibody response in saliva was mainly directed to the V4 region (aa 385-409) and a more C-terminal part of the V3-region (aa 325-344) compared with the IgG response, which predominantly was directed to a more central part of the V3 loop (aa 308-325). A similar picture was seen for immunoglobulins of the two isotypes derived from serum. We have in this study shown IgA epitope-specific immune response within HIV-1 gp160, indicating that antibodies of IgA isotype may recognize somewhat different antigenic domains compared to IgG antibodies.     

Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1-infected patients

Memory B cells are long-living cells that circulate throughout the body and differentiate into plasma cells after stimulation by antigens, cytokines, and direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients, we assessed whether in vitro polyclonal B cell activation that induces immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B cells to synthesize antibodies specific to HIV-1. To this end, highly purified B cells from 10 HIV-1-untreated patients were cultured with or without mouse fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10. The percentage of immunoglobulin SCs we obtained by using the B cell-CD40L stimulation system was equal to 55% to 98% of the circulating memory B cells. Moreover, the anti-HIV-1 IgG, IgA, or IgM antibody SCs represented 1 x 10-2 to 1 x 10-3 of the total immunoglobulin SCs. The anti-HIV-1-specific antibodies detected in cell culture supernatants were directed to gag-, pol-, and env-encoded viral proteins. We found that in AIDS patients, HIV-1-specific resting memory B cells circulate in the blood and can be quantified by their anti-HIV-1 antibody secretion after strong B cell polyclonal stimulation.     

The neonatally thymectomized rat: a model for compensatory IgM antibody formation in exocrine secretions.

The effect of T-cell deprivation on IgM antibodies in saliva was studied in rats. IgM was never detected in salivas obtained from normal or sham-thymectomized rats, but was detected in saliva samples from 8/15 (53.3%) rats that had undergone neonatal thymectomy. All (6/6) neonatally thymectomized rats exhibited an IgM antibody response to DNP in salivary secretions after local immunization with a T-dependent antigen (DNPBGG), while no IgA anti-DNP activity was detected in saliva from these antimals. IgM antibodies were detected in saliva from 5/7 thymectomized rats following local injection with a T-independent antigen (DNP-Lys-Gicoll). This was accompanied by detectable but substantially reduced levels of secretory IgA antibody in saliva from 7/7 rats. The results suggested that absent or decreased salivary IgA responses accompanying T-cell deprivation in the rats are compensated for by secretion of IgM antibodies into the saliva. The neonatally thymectomized rat may thus provide a model for the study of synthesis, secretion and protective potential of exocrine IgM antibodies.     

Inadequacy of musocal IgM antibodies in selective IgA deficiency: Excretion of attenuated polio viruses is prolonged

A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 in order to cease an outbreak of poliomyelitis. We followed eight IgA-deficient individuals and nine controls for poliovirus excretion in feces and for antibody responses in serum and saliva. Five weeks after oral poliovirus vaccination all eight IgA-deficient individuals were still excreting polioviruses, in contrast to one of nine controls. The concentration of polioviruses, as estimated by a semiquantitative immunofluorescent assay, was generally higher and the test was significantly more often positive in the samples from the IgA-deficient individuals. Although serum levels of antibodies to poliovirus type 3 were lower in IgA-deficient individuals before vaccination, both measurements showed that the two groups had similar antibody levels 4 weeks after vaccination. IgA-deficient individuals lacked salivary IgA antibodies to poliovirus types 1 and 3 but had increased levels of IgM antipolio antibodies, which were shown to carry secretory component. We conclude that the mucosal IgM antibodies of IgA-deficient individuals eliminate polioviruses less efficiently than do the IgA antibodies of normal individuals.     

Quantification of IgA and IgG and specificities of antibodies to viral proteins in parotid saliva at different stages of HIV-1 infection

Paired sera and parotid saliva from 75 HIV-1-infected patients, divided in three equal groups with CD4⁺ cell counts > 500, 200–500 and < 200/mm³, respectively, were analysed for IgG, IgA and secretory IgA (sIgA) concentrations and for IgG and IgA antibody directed to HIV-1. Twenty-nine age-matched HIV⁻ subjects were used as controls. In serum the concentrations of immunoglobulins were significantly increased in HIV-infected subjects compared with controls, and a progressive increase of IgA and sIgA was noticed while the CD4⁺ cell count decreased. In contrast, concentrations of IgA and sIgA were not different in parotid saliva between the four subject groups. By an ELISA test directed towards HIV-1 proteins, 73 of the 75 serum specimens from the HIV-infected subjects (97%) and 43 of the corresponding saliva (57%) were found positive for specific IgA antibodies to HIV-1, with an even distribution among the three groups of patients. By Western blotting multiple specificities of IgA to HIV-1 proteins were not frequently found in patients. By contrast, in spite of an IgG concentration in saliva about 100 times lower than that of IgA, reactivities were significantly higher for IgG than for IgA antibodies, especially to env and to pol HIV-1 products. Altogether, these data suggest that the regulation of IgA production in HIV-infected subjects is independent in serum and in parotid saliva. This imbalance of IgA/IgG antibodies to HIV-1 at the mucosal level appears to be a specific feature of HIV-1 infection, and may raise important issues in terms of local protection after immunization.     

Diagnosis of dengue virus infection by detection of specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva

To evaluate alternative approaches to the serological diagnosis of dengue virus (DEN) infection, the detection of DEN-specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva specimens was assessed in 147 patients with symptoms of DEN infection seen at the Ministry of Health in Nicaragua. Seventy-two serum samples were determined to be positive for anti-DEN antibodies by IgM capture enzyme-linked immunosorbent assay, the routine diagnostic procedure. Serum and saliva specimens were obtained from 50 healthy adults as additional controls. IgM was detected in the saliva of 65 of the 72 serum IgM-positive cases, 6 of the 75 serum IgM-negative cases, and none of the control group, resulting in a sensitivity of 90.3% and a specificity of 92.0% and demonstrating that salivary IgM is a useful diagnostic marker for DEN infection. Detection of IgA in serum may be another feasible alternative for the diagnosis of DEN infection, with serum IgA found in 68 (94.4%) of the IgM-positive cases. In contrast, detection of IgA in saliva was not found to be a useful tool for DEN diagnosis in the present study. Further studies of the kinetics of antibody detection in another set of 151 paired acute- and convalescent-phase serum samples showed that DEN-specific IgA antibodies were detected in more acute-phase samples than were IgM antibodies. Thus, we conclude that DEN-specific IgA in serum is a potential diagnostic target. Furthermore, given that saliva is a readily obtainable, noninvasive specimen, detection of DEN-specific salivary IgM should be considered a useful, cheaper diagnostic modality with similar sensitivity and specificity to IgM detection in serum.     

Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva

To evaluate alternative approaches to the serological diagnosis of dengue virus (DEN) infection, the detection of DEN-specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva specimens was assessed in 147 patients with symptoms of DEN infection seen at the Ministry of Health in Nicaragua. Seventy-two serum samples were determined to be positive for anti-DEN antibodies by IgM capture enzyme-linked immunosorbent assay, the routine diagnostic procedure. Serum and saliva specimens were obtained from 50 healthy adults as additional controls. IgM was detected in the saliva of 65 of the 72 serum IgM-positive cases, 6 of the 75 serum IgM-negative cases, and none of the control group, resulting in a sensitivity of 90.3% and a specificity of 92.0% and demonstrating that salivary IgM is a useful diagnostic marker for DEN infection. Detection of IgA in serum may be another feasible alternative for the diagnosis of DEN infection, with serum IgA found in 68 (94.4%) of the IgM-positive cases. In contrast, detection of IgA in saliva was not found to be a useful tool for DEN diagnosis in the present study. Further studies of the kinetics of antibody detection in another set of 151 paired acute- and convalescent-phase serum samples showed that DEN-specific IgA antibodies were detected in more acute-phase samples than were IgM antibodies. Thus, we conclude that DEN-specific IgA in serum is a potential diagnostic target. Furthermore, given that saliva is a readily obtainable, noninvasive specimen, detection of DEN-specific salivary IgM should be considered a useful, cheaper diagnostic modality with similar sensitivity and specificity to IgM detection in serum.     

Isotype profiles of anti-gp160 antibodies from HIV-infected patients in plasma and culture supernatants

We studied isotype profiles of anti-HIV antibodies (Ab) in HIV-1-infected African patients with high viral loads and major B cell dysfunction. We focussed on IgG1, IgG3, and IgA as these classes and subclasses tend to support neutralizing functions against HIV. Total IgG1, IgG3 and IgA were detected in the plasma of both HIV-1-infected and HIV-negative African individuals, but there was significantly more IgG3, a rare subclass, in HIV-1-infected patients (P < 0.05). Anti-HIV-gp160 specific antibodies were detected in sera from nearly all HIV-1-infected individuals tested, but not in HIV- individuals: 10/10, 9/10 and 8/10 individuals displayed specific IgG1, IgG3 and IgA, respectively. In the corresponding PBMC cultures carried out in the presence of IL-10 and IL-2, there was specific IgG1 and IgA in 5/10, and 3/10, respectively, but no IgG3 was detected. When HAART-treated European HIV-infected PBMC cultures were tested using the same protocol, specific IgG3 was detected in 4/10 cultures, and was unaffected by the addition of soluble CD40L molecules. The present study thus shows that, despite lymph node disorganization in HIV-infected drug-na?ve Africans, these individuals retain the ability to produce HIV-specific IgG1, IgG3 and IgA. However, the specific mechanisms controlling the selective production of IgG3, probably the most potent subclass and a potential target of immuno-intervention, warrants further investigation.     

IgA and IgM rheumatoid factors in serum, saliva and other secretions: relationship to immunoglobulin ratios in systemic sicca syndrome and rheumatoid arthritis.

Paired serum and saliva samples from seven patients with systemic sicca syndrome (SSS), 15 patients with rheumatoid arthritis and a positive Schirmer's test (RA+), 15 patients with rheumatoid arthritis and negative Schirmer's test (RA-) and 14 normal individuals were analysed for albumin and immunoglobulin concentration as well as IgA and IgM rheumatoid factor (RF) activity. Protein levels in saliva were higher in SSS and RA+ but, when corrected for serum concentration and salivary flow rate, only the IgG ratio remained significantly elevated in SSS (P less than 0.01) and RA- (P less than 0.05) and the IgM ratio was reduced in RA- (P less than 0.05) compared to controls. Although IgM RF activity in serum and saliva was strongly correlated (P less than 0.001) in all three patient groups, the activity in saliva was considerably lower than serum activity. In the two (RA) patients tested, IgM RF in saliva contained secretory component. Mean salivary IgA RF activity varied between 34% (RA-) and 84% (SSS) of serum activity and correlated with serum activity in SSS (P less than 0.001) and RA- (P less than 0.01). IgA RFs in saliva, but not in serum, contained secretory component. Additional demonstration of IgA RF activity in nasal and duodenal secretions in SSS may be related to involvement of the common mucosal immune system.     

Salivary immunoglobulin A and serum antibodies to Streptococcus mutans ribosomal preparations in dental caries-free and caries-susceptible human subjects

Caries-free subjects or individuals with low caries susceptibility exhibited significantly higher (P less than 0.001) levels of naturally occurring salivary immunoglobulin A (IgA) and serum IgG, IgA, and IgM antibodies to a Streptococcus mutans ribosomal preparation than subjects with high caries susceptibility. Absorption of saliva and serum samples with S. mutans ribosomal preparations, but not with other S. mutans antigens or with Escherichia coli and Neisseria gonorrhoeae ribosomal preparations, removed the antibody activity. Absorption with Streptococcus sanguis ribosomes and NH4Cl-washed S. mutans ribosomes partially removed the anti-S. mutans ribosome antibody activity. These results provide evidence that naturally occurring salivary and serum antibodies to the S. mutans ribosomal preparation correlate with susceptibility to dental caries.     

Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease

Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29). Non-specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme-linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva. Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (P < 0.01). Salivary IgA (and IgG) levels were raised in OFG and OFG + CD (P < 0.01) but not in the CD group. Parotid IgA was also raised in OFG and OFG + CD but not in CD. The findings suggest that serum IgA changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity. Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG. Serum IgA antibodies to S. cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C. albicans were elevated significantly in all three patient groups (P < 0.02). No differences were found with antibodies to S. mutans. Whole saliva IgA antibodies to S. cerevisiae (and C. albicans) were raised in the groups with oral involvement. These findings suggest that raised serum IgA antibodies to S. cerevisiae may reflect gut inflammation while raised SIgA antibodies to S. cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease. Analysis of salivary IgA and IgA antibodies to S. cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement.     

Saliva secretory IgA antibodies against molds and mycotoxins in patients exposed to toxigenic fungi

Upper respiratory exposure to different environmental antigens results first in the activation of mucosal immunity and production of IgA antibodies in different secretions including saliva. Despite this there is no study, which addresses secretory antibodies against molds and mycotoxins. The purpose of this study was to evaluate mold-specific salivary IgA in individuals exposed to molds and mycotoxins in a water-damaged building environment. Saliva IgA antibody levels against seven different molds and two mycotoxins were studied in 40 patients exposed to molds and in 40 control subjects. Mold-exposed patients showed significantly higher levels of salivary IgA antibodies against one or more mold species. A majority of patients with high IgA antibodies against molds exhibited elevation in salivary IgA against mycotoxins, as well. These IgA antibodies against molds and mycotoxins are specific, since using molds and mycotoxins in immune absorption could reduce antibody levels, significantly. Detection of high counts of molds in water-damaged buildings, strongly suggests the existence of a reservoir of mold spores in the environment. This viable microbial activity with specific mold and mycotoxin IgA in saliva may assist in the diagnosis of mold exposure. Whether mold and mycotoxin specific IgA antibodies detected in saliva are indicative of the role of IgA antibodies in the late phase of type-1 hypersensitivity reaction or in type-2 and type-3 delayed sensitivities is a matter that warrants further investigation.