Received Date: February 26, 2013; Accepted Date: March 22, 2013; Published Date: March 26, 2013
Citation: Noorbakhsh S, Farhadi M, Daneshi A, Tabatabaei A, jomeh EH, et al. (2013) Associations Between Antibodies Against the Endothelial Cell and T. gondii; Cytomegalovirus in Serum of Children with Cochlear Implant Surgery. J AIDS ClinRes 4:197. doi:10.4172/2155-6113.1000197
Copyright: © 2013 Noorbakhsh S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Background: Cytomegalovirus (CMV) and T. gondii are two common causes of SNHL (Sensorineural hearing loss) in Iranian children. Immune-mediated vascular damage induced by endothelial cell antibodies may have a prominent role in sensorineural hearing loss. Objectives: To determine the serum CMV and T. gondii antibodies against endothelial cell in children with profound SNHL and cochlear implant surgery.
Materials & Methods: A cross sectional study was performed on 76 cases with severe SNHL (mean age 32 ± 30.6 months) at cochlear implant ward of Rasoul hospital, Tehran Iran (2008-2010). The titers of antibodies against endothelial cell (Indirect immunofluorescence assay); were determined in sera of 66 cases. Specific antibodies (IgG & IgM) against T. gondi, CMV (Enzyme linked immunosorbent assay) determined in Idiopathic SNHL cases.
Results: Idiopathic type of SNHL was diagnosed in 28.8% (19/66) of younger cases (mean age=20 months; PV=0.05). Positive AECAs was detected in 14.4% (11/76) of cases (with mean age 50 vs. 32 months in cases with negative test; P value=0.047). Positive AECAs had not significant differences between Idiopathic and Non idiopathic type of SNHL [10.5% vs. 9%; PV=0.1]. Positive AECAs were more frequent in cases with known postnatal infections (e.g. mumps, meningitis, chicken pox, etc.) in comparison with non-infection cases (P-value=0.05). Positive T. gondii -IgM (recent infection) was found in 8 /19 (%42); 1 case also had positive T. gondii -IgG. Positive CMV-IgM &IgG were determined in 10 /19 (%52); 17/19 (%89) respectively. A meaningful correlation was observed between positive AECAs and those infections (Toxo, CMV) in Idiopathic (and unclassified) SNHL cases.
Conclusion: Idiopathic type of SNHL with a poor outcome is common (28.8%) in children with cochlear implant surgery Positive AECAs cases had not differences between 2 type of SNHL but were more frequent in older cases with known postnatal infections (meningitis, mumps, chicken pox etc.). A good correlation (p=0.05) between the positive AECAs and known infections determined in studied cases. In contrast, those younger cases (<3 years) with positive AECAs had recent CMV /or T. Gondii (Positive IgM) infections (23 %; 17.7%) without known congenital or acquired type of infections. At least in our country, in younger SNHL cases (<2 year old) due to confirmed recent CMV or T. Gondii infections, application of specific drugs are preferred. Immunosuppressive therapy is only recommended in older cases (>2 year old) with Idiopathic SNHL and concomitant positive AECAs.
Sensory neural hearing loss (SNHL); Cochlear implant; Anti-endothelial cell antibodies (AECAs); CMV; T. Gondii
The incidence of unilateral hearing loss in children was approximately 0.1 %. In 7.5% of cases unilateral deafness were diagnosed accidentally, most often between the 7th and the10th decades of age . The etiology of most of these cases remains unknown. Neither children nor their parents can precisely determine the time of its appearance, especially when it is not accompanied by other symptoms, such as dizziness or tinnitus . Infants hospitalized in Neonatal Intensive Care Units (NICU) are at higher risk for SNHL [3,4]. The overall incidence of inner ear abnormalities in children with SNHL evaluated by MRI is 40%. Children with unilateral hearing loss have a greater percentage of inner ear anomalies than children with bilateral SNHL . Asymptomatic or symptomatic course of mumps, CMV, T. gondii and measles should also be taken into consideration as causes of SNHL in children. Autoimmune hearing loss as a plausible explanation for a certain percentage of the group is categorized as Idiopathic type. SNHL in children can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Many studies established the non-specific auto-antibodies vs. the inner ear, such as anti endothelial cell antibodies (AECAs). AECAs have a prognostic factor for these diseases and can be considered a useful clinical tool for differentiating patients with idiopathic hearing loss [6-8].
Cadoni et al. investigated the presence of AECAs and its role in causing damage to the stria vascularis in immune-mediated sensorineural deafness . The appearance of endothelial cell antibody is related to the poor outcome of hearing loss [10-16].
Congenital CMV is the most common cause of congenital infections in the world [23-25]. In last decade, role of CMV and T. Gondii infections in children with SNHL had been proved in our center [26,27].
Main goal of this study was to determine associations between serum AECAs and antibodies against CMV and T. Gondii in children with profound SNHL (cochlear implant surgery) in our center.
This case – control study was performed in cochlear implant center of Rasul Akram Hospital in Tehran from 2008 to 2010.
Cases consisted of 75 children with Severe SNHL (<95 db) which were candidate for cochlear implant surgery. This study was approved by the Ethical Committee in Research Center of ENT, Head and Neck Surgery & Research Center of Pediatric Infectious Diseases in Tehran University of Medical Sciences. Initially, a questionnaire was completed by an authorized physician for each case and control.
Audiologic screening (Auditory Brainstem Response, Evoked Ottoacoustic Emissions and Pure Tone Audiometry) appropriate for age was used in all cases. Diagnostic parameters for SNHL were based on AAO (American academy of Otolaryngology criteria). Idiopathic and Non idiopathic type of SNHL were diagnosed in all cases.
Blood samples (2 ml) were centrifuged and transferred to our research laboratory. All sera were kept frozen at -80°C until usage. AECAs (IgG) searched in serum by Indirect Fluorescent Antibody Test (KMI diagnostics, US); ELISA assay was used for searching the specific IgM and IgG antibodies against CMV, T. Gondii (Bio chem Immuno Systems, Italy). The results were calculated qualitatively as suggested by the manufacturer. In order to minimize the false-positive interferences with anti-endothelial cell antibodies (AECAs), Rheumatoid factors (RFs) and antinuclear antibodies (ANAs) titers followed in serum samples in the cases. All positive individuals for RFs & ANAs (5 cases and 3 controls) were excluded.
The Student t-test was used to determine significant differences in means for all continuous variables. Chi-square values (CI: 95%; P<0.05) were calculated for all categorical variables. P value less than 0.05 was considered significant. All analyses were conducted using SPSS version 11.5.
The age range in SNHL cases (n=75) were between 3 to 168 months (mean=33.6 ± 38.6 months). 50% (37/74) were male and 50% (37/74) were female (missing=2).
Positive AECAs were detected in 14.5% (11/75) of SNHL cases; AECAs were seen in cases aged >5 years in comparison with cases <5 years old (PV=0.047). The mean age of children with positive AECAs was higher (50 vs. 32 months=0.05). Positive AECAs had no differences between Idiopathic (and unclassified); and Non Idiopathic type of SNHL [10.5% (2 /21) vs. 9% (4/47) PV=0.1]. Positive AECAs were more frequent in cases with known postnatal infections infections (e.g.: mumps, meningitis, chicken pox, etc.) in comparison with noninfections cases (P-value=0.05) (Table 1).
|SNHL cases (Mean age = 33.6 months) Missed (Unclassified=8)||Idiopathic SNHL (28%) (Mean age = 20 months)||Non Idiopathic SNHL (%71.2) (Mean age = 45 months )||P value=0.05|
|Positive AECAs 11/75 (%14.4)||2 /19 (%10.5)||4/47 (%9)||P value =0.1|
|Positive T. Gondii IgM 8 /45(%17.7)||Positive T. Gondii IgM 8 /19 (%42)||------||----|
|Positive CMV IgM 10 /45 (%23)||Positive CMV IgM 10 /19 (%52)||------||------|
Table 1: Comparing the AECAs and T. Gondii /CMV antibodies between SNHL cases.
Idiopathic type of SNHL was diagnosed in 28.8% (19/66) of cases. Non Idiopathic SNHL (e.g. familial, kernicterus, prematurity, hypoxic ischemic, infections etc.) was diagnosed in 71.2 % (47/66); missing (unclassified) reported in 8 cases. Mean age of Idiopathic SNHL cases was lower than Non Idiopathic type (20 vs. 45 months; P=0.05) .Positive AECAs had no differences between Idiopathic and Non Idiopathic type of SNHL [10.5% (2 /19) vs. 9% (4/47), p=0.1]
Searching the sera for infections had done for all idiopathic cases. Positive T. Gondii -IgM (recent infection) was found in 8/19 (%42); 1 case also had positive T. Gondii -IgG. Positive CMV-IgM and IgG were determined in 10/19 (%52); 17/19 (%89) respectively. A meaningful correlation was observed between positive AECAs and those infections (Toxo, CMV) in Idiopathic (and unclassified) SNHL cases.
In present study, 30% (19/76) of studied children were diagnosed as Idiopathic type of SNHL which is very close to 38.7% reported by other authors [1-4]. Idiopathic SNHL cases were younger than Nonidiopathic type (20 vs. 45months).
On the other hand, Results of this study is far from Cadonni et al.  study in adults; they reported the higher positive AECAs (54%) in SNHL cases than control group (P=0004).
Positive AECAs were not different between Idiopathic and Non idiopathic type of SNHL [10% vs. 9%, P=0.1). Cases with positive AECAs were older than 5 years (Fisher’s Exact Test=0.047).
Although positive AECAs were not significantly different between 2 types of SNHLs, But definite postnatal infectious causes (meningitis, mumps, chicken pox, etc.) and recent T. gondii and CMV infection were observed in Non-Idiopathic type of SNHL with positive AECAs (>5year old).
Positive T. gondii -IgM (recent infection) was found in 17.7% of cases (8 /45); 1 case (2.2 %) had positive T. gondii –IgG (previous infection). Positive CMV-IgM &IgG were 11/45 (23 %), 23/45 (51%) respectively.
Post or prenatal (usually indolent) T.Gondii /CMV infections were frequent in present study. Recent CMV infection (positive IgM) in 23% and recent T.Gondii infection in 17.7% of idiopathic (and unclassified) type of SNHL cases. These results are very close to previous serologic study in our center [26-29]. Recent CMV and T. Gondii infections (positive IgM) in SNHL cases (mean age=35 months) were 34.6% and 11.5%, respectively. But other infections (Mumps, Rubella, Herpes type-1) were rare . The previous study in all type of SNHL in our center had similar results . Recent T.Gondii infection (IgM) detected in none of normal controls in compare with 12% of SNHL cases (P value=0.00), but previous immunity (IgG) against T.Gondii infection was significantly higher in the control healthy group (48% vs 21%; P value <0.001) .
In addition to postnatal infectious diseases (mumps; chicken pox; severe sepsis, otitis media, etc.) which were observed in cases, an excellent correlation was seen between positive AECAs and positive antibodies against T. gondii/CMV in Idiopathic type of SNHL (mean age: 22 months). T. gondii infection was defined as the most common infection with positive AECAs. Congenital (or acquired) Toxo/CMV infections might have role in younger cases with Idiopathic type of SNHL (<2 years).
Role of CMV in pathogenesis of SNHL in children have been reported in many countries as well as Iran. Correlation between proven infection and positive AECAs does not mean the cause and effect in studied cases.
Positive AECAs in older Idiopathic SNHL cases (>5year) could define the clinical associations of AECAs with immune-mediated inner-ear disorders. Probably AECAs after infancy period might play a prominent role in causing damage to the stria vascularis in immunemediated SNHL. Multiple potential mechanisms can result in immunemediated inner ear disease in children. Except one study in children, other previous studies had been done in adults . The association of AECAs with endothelial injury in the course of these diseases prompted us to develop assays for these antibodies in clinical practice. Prognostic factors for Idiopathic SNHL in adults were reported by many authors [10-14].
Production of serum AECAS would be as a marker of disease activity. Cvorovic et al. reported the appearance of AECAs is related to the poor outcome and absent recovery of hearing loss in adults .
Due to poor outcome of Idiopathic SNHL in children, we recommend to search not only the serum AECAs, but also specific antibodies against indolent CMV/T.Gondii infections in the cases. Idiopathic type of SNHL observed in lower age (< 2 years old) might have congenital (or acquired) Toxo/CMV infections which can induce progressive hearing loss. Fortunately both infections are treatable by specific oral drugs. Decisions for immunosuppressive therapy in older children need a randomized clinical trial in future.
Strength of the study
Correlation between indolent CMV/T.Gondii infections and AECAs in children with Idiopathic type of SNHL has not been studied up to now. Most previous studies done in adults but not in children especially in Idiopathic type of SNHL.
Small population especially in younger age (<2 year old) in present study is an important limitation. Other infectious agents (influenza, measles, mumps, varicella etc.) were not studied in our cases.
Idiopathic type of SNHL with a poor outcome is common (28.8%) in children with cochlear implant surgery Positive AECAs cases had not differences between 2 type of SNHL but were more frequent in older cases with known postnatal infections (meningitis, mumps, chicken pox etc.). A good correlation (p=0.05) between the positive AECAs and known infections determined in studied cases. In contrast, those younger cases (<3 years) with positive AECAs had recent CMV /or T. Gondi (Positive IgM) infections (23 %; 17.7%) without known congenital or acquired type of infections. At least in our country, in younger SNHL cases (<2 year old) due to confirmed recent CMV or T. Gondi infections, application of specific drugs are preferred. Immunosuppressive therapy is only recommended in older cases (>2 year old) with Idiopathic SNHL and concomitant positive AECAs.
This study was supported by the ENT, Head and Neck & Surgery, and Research Center of Pediatric Infectious Diseases in Tehran University of Medical Sciences.