Table 1.
Studies assessing the expression of antibodies in otitis media.
| Authors and Reference | Study Design | Species/Type of OM | Type of Samples or Specimens | Detection Methods | Targets | Results/Conclusion |
|---|---|---|---|---|---|---|
| Virgil et al. [37] | Prospective study | Human (255 specimens of MEF from 165 episodes of AOM in children) | MEF vs. serum | Radial immunodiffusion | IgG, IgM, IgA | IgA: MEF > serum in almost half the patients - over 9 months of age: culture(−) was dominant in case of MEF > serum IgA IgG and IgM: MEF < serum The MEF of AOM represents primarily a secretory response to inflammation rather than a transudate. |
| Sloyer et al. [38] | Prospective study | Human (61 AOM childrenl) | MEF, serum | IFA, IHA | IgG, IgM, IgA (pneumococcal Ab serotype 1, 3, 6, 14, 18, 19, and 23) | Serum: IgG, IgM: predominantly detected MEF: equally detected all three classes Approximately 25% of the patients (16 of 61) had a positive immune response to their infection as evidenced by increased levels of pneumococcal antibody in the convalescent serum. |
| Sloyer et al. [39] | Prospective study | Human (40 AOM children) | MEF, serum | IFA, IHA | IgG, IgM, IgA (Ab to Hi) | Serum: IgG> IgM = Ig A: acute phase < convalescent phase MEF: IgG = IgA > IgM |
| Sloyer et al. [40] | Prospective study | Human (103 AOM childrenl) | MEF, serum | IFA, radial immunodiffusion | IgG, IgM, IgA (antibody to measles, mumps, rubella, and polio-1) | IgA: MEF > serum IgG: MEF < serum Mean specific MEF IgA titer: immunized > unimmunized |
| Sloyer et al. [33] | Prospective study | Human (80 patients with AOM) | MEF (cleared vs. not cleared) | Indirect fluorescent antibody, radioimmunoassay | IgG, IgM, IgA (Hi, Spn) | Abs concentration: cleared MEF > not cleared MEF Clearing of the MEF in patients with AOM due to Spn or Hi was significantly associated with the presence and concentration of specific Abs in the MEF at the time of diagnosis. |
| Ren et al. [41] | Prospective study | Human: 35 AOM and 149 controls | Serum | Western blot, ELISA | Serum Ab response to Mcat (OMP CD, OppA, Msp22, Hag and PilA2) | Serum IgG in all cases: Msp22 = OppA > OMP CD = Hag = PilA2. Serum antibody to Mcat increased with age in naturally immunized children age 6–30 months following Mcat NP colonization and AOM. In AOM group: IgG against OMP CD: acute phase < convalescent phase High antibody levels against OppA, Msp22, and Hag correlated with reduced carriage. |
| Kaur et al. [42] | Prospective cohort study | Human (137 AOM) | Serum, MEF, NW | ELISA, Western blot | IgG, IgA, sIgA | IgG: NW < MEF ≈ serum IgA: NW > MEF ≈ serum sIgA: MEF (+) IgA in MEF: originated from serum > NW |
| Kaur et al. [43] | Prospective study (3.5 years) | Human: 34 AOM vs. 35 rAOM vs. 25 AOMTF | Serum | ELISA | Serum IgG antibody titers of 5 different Spn proteins (PhtD, LytB, PcpA, PhtE, and Ply) | (1) Acute phase: IgG to PhtD, LytB, PhtE, Ply: rAOM < AOM = AOMTF (2) Convalescent phase: IgG to PhtD, LytB, PhtE, Ply: rAOM = AOMTF < AOM Otitis-prone and AOMTF children mount less of an IgG serum antibody response as compared with non-otitis-prone children to Spn proteins after AOM. |
| Kaur et al. [44] | Prospective study (3.5 years) | Human: 26 AOM vs. 32 rAOM vs. 27 AOMTF | Serum | ELISA | Serum Ab response to outer membrane protein D, P6, OMP26 of NTHi | (1) Acute phase: IgG against PD: rAOM < other two groups IgG against P6, OMP26: rAOM < AOMTF (2) Convalescent phase: rAOM and AOMTF: no change in total IgG against all the three proteins AOM: increased to PD The data on acute sera of otitis prone vs. non-otitis prone children and the acute-to-convalescence response in non-otitis prone children point to a possible link of anti-PD to protection. Further, otitis prone children should be evaluated for their responses to PD, P6, and OMP26 vaccine antigens of NTHi. |
| Veenhoven et al. [34] | Prospective study | Human (365 AOM children: rAOM vs. non-rAOM) | Serum | radial immunodiffusion | IgG (IgG1, IgG2), IgM, IgA | IgG (IgG1, IgG2), IgM, IgA: rAOM < non-rAOM In rAOM groups (compared with normal value): IgG, IgM, IgA, IgG1; increased levels IgG2: decreased levels Lower Ig levels in rAOM children suggest a generalized decreased Abs response in rAOM children. |
| Corscadden et al. [45] | Cross-sectional study | Human (166 rAOM children vs. 61 healthy controls) | Serum, MEF | multiplex bead-based assay, microsphere-based flow cytometric assay | IgG, IgG1, and IgG2 (against 11 pneumococcal polysaccharides: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F 1) |
IgG and IgG1 against serotype 5: rAOM > control All pneumococcal serotype specific IgG in rAOM: serum = MEF |
| Wiertsema et al. [46] | Cross-sectional study | Human (172 rAOM vs. 63 controls) | Serum | Multiplex bead assay | IgG: against 4 pneumococcal (PspA1, PspA 2, CbpA, and Ply) and 3 NTHi (P4, P6, and PD) | IgG against NTHi P4, P6, PD: rAOM > control IgG against pneumococcal protein antigens: rAOM ≈ control |
| Krakau et al. [47] | Prospective study | Human: 28 adults with low IgG2 level during childhood (15: a history of rAOM during childhood vs. 13 controls) | Serum | Nephelometry, ELISA | total IgG and IgG subclasses 1–4 | All Igs: rAOM = control Study subjects who had rAOM combined with low IgG2 levels during childhood had a normalized immunoglobulin pattern as adults. |
| Freijd et al. [48] | Prospective study | Human (15 pOME children vs. 15 age matched healthy control children vs. 15 healthy adults) | Plasma samples | ELISA | Spn Abs of different IgG subclasses | Adults: IgG1 < IgG2 Children: IgG1 > IgG2 (pOME < control) |
| Verhaegh et al. [49] | Prospective cohort study | Human (rAOM vs. cOME) | Serum, MEF | Luminex xMAP technology | IgG, IgM, IgA (against Spn and Mcat) |
Serum and MEF antigen-specific IgG, IgM, IgA: rAOM ≈ cOME Serum or MEF IgG, IgM, IgA level were not different and not related to bacterial identification in both groups Serum and MEF show strong correlation for only IgG in both groups |
| Shin et al. [50] | Prospective study | Human (29 p-OME vs. 32 OME children) | MEF | ELISA | IgG, IgM, IgA | IgA: pOME < OME. Lower concentrations of IgA in middle ear fluid of patients with OME may be related to OME recurrence and chronicity. |
| Yamanaka et al. [51] | Prospective study | Human (320 OME ears: acute, 10.3%; subacute, 16.6%; chronic, 73.1%) | MEF | ELISA | IgG, IgM, IgA | IgG-ICs: highest positive rate was found in acute cases IgA-ICs: highest positive rate was found in subacute cases neutrophil dominant type in chronic cases: highest IgG-ICs level ICs formed in the MEF might play an important role in the prolonged inflammatory process of OME through the complement activation following chemotaxis of neutrophils. |
| Yeo et al. [52] | Prospective study | Human (58 cOME vs. 64 controls) | MEF, serum | ELISA, nephelometry | IgG, IgM, IgA | Serum IgG, Ig M, IgA: cOME < control MEF Ig concentration–the presence of bacteria: no correlation MEF Ig concentration–serum Ig concentration: no correlation Serum Ig concentration: bacteria (+) > bacteria (−) The presence of effusion bacteria in OME may be related to systemic immunity, but the concentration of Ig in effusion fluid may not be affected by the presence of effusion bacteria. |
| Drake-Lee et al. [53] | Two age-matched cohorts study | Human (50 OME vs. 50 age-matched controls) | Serum | ELISA, radial immunodiffusion | Total IgG, IgG subclass, total IgA, IgA subclass | Total IgA, IgA2, total IgG, IgG2: OME ≈ control normal antibody response between both groups of patients. |
| Chung et al. [54] | Prospective study | Human (27 mucoid OME vs. 18 serous OME) | MEF | Immunoblot assay | sIgA | sIgA: mucoid OME > serous OME |
| Takada et al. [55] | Prospective study | Human (59 OME children) | MEF, serum | ELISA | IgG, IgM, IgA, and sIgA antibodies specific to outer membrane antigens of Mcat | Serum: IgG > IgA > IgM MEF: IgG > IgM > sIgA > IgA All Ig: MEF > serum IgG and IgM in MEF: acute phase > subacute/chronic phase sIgA in MEF: acute phase < subacute/chronic phase IgG in serum or MEF: recurrent/persistent OME group < nonrecurrent/non-persistent OME group Decreased serum and MEF IgG antibody levels specific to outer membrane antigens of Mcat may lead to failure to eliminate this organism, resulting in persistent and/or recurrent appearance of MEF. |
| Faden et al. [56] | Prospective study | Human (14 OME) | Serum, MEF | Ab assay by 96-well microtiter plate | IgG, IgM, IgA | Serum: IgG > IgM > IgA MEF: IgG > IgA > IgM The IgG- and IgA-specific antibody present in middle ear effusions appeared to represent local production rather than passive diffusion from the systemic circulation. |
| Lasisi et al. [57] | Prospective study | Human (20 cSOM vs. 17 aSOM vs. 15 controls) | MEF, serum | ELISA | IgG, IgM | Serum IgG: cSOM > control > aSOM MEF IgG: cSOM > aSOM Serum IgM: aSOM > cSOM> control MEF IgM: aSOM > cSOM |
| Lasisi et al. [58] | Prospective study | Human: 20cSOM vs. 17 aSOM vs. 15 controls | Serum, MEF | Radial immunodiffusion | IgE | Serum IgE: cSOM > aSOM > control MEF IgE: cSOM > aSOM MEF/serum IgE ratio: cSOM > aSOM Serum and MEF showed correlation in cSOM. Allergy appears to play a contributory role in CSOM and elevated IgE in the MES suggests a likely mucosal response. |
OM, otitis media; MEF, middle ear fluid; Ig, immunoglobulin; AOM, acute otitis media; p-OME, prone-otitis media with effusion; OME, otitis media with effusion; ELISA, enzyme-linked immunosorbent assay; ICs: immune complexes; Hi, Haemophilus influyenzae; Spn, Streptococcus pneumoniae; Abs, antibodies; Mcat, Moraxella catarrhalis; sIgA, secretory IgA; rAOM, recurrent acute otitis media; cOME, chronic otitis media with effusion; cSOM, chronic suppurative otitis media; aSOM, acute suppurative otitis media; IFA, indirect fluorescent antibody test; IHA, indirect hemagglutination; rAOM, recurrent acute otitis media; PspA, Streptococcus pneumoniae antigens pneumococcal surface protein A family; CbpA, choline binding protein A; Ply: pneumolysin; NTHi, nontypeable Haemophilus influenza; P4, Protein 4; P6, Protein6; PD, Protein D; AOMTF, acute otitis media treatment failure; OMP, outer membrane protein; OppA, oligopeptide permease A; Hag, hemagglutinin; Msp, Moraxella surface protein; PilA2, PilA clade 2; Pht, pneumococcal histidine triad proteins; LytB, a murein hydrolases; PcP, a choline binding protein; NW, nasal wash.