please rephrase the next paragraphs " In Aguilera et al. [13] study, regarding ABGA are supported by one single measuring method, so positive findings with other methodology cannot be ruled out. The frequency of ABGA in their nc-ADHD patients (3%) was like that found in control samples of other studies (0%-5%), with the same semi-quantitative ELISA method [12, 18]. Conversely, they were able to detect ABGA positivity in patients with acute onset of tics or OCD (27%), comparable with other studies [34]. These patients with positive ABGA had also some evidence of recent GAS infection, including improvement of symptoms following penicillin treatment in one patient. These findings support the reliability of the used technique. Contrary to Aguilera et al. [13], some authors have found positive ABGA together with high titers of anti-streptococcal antibodies in nc-ADHD participants. Kiessling et al. [35] reported 37% of ABGA positivity in 19 nc-ADHD patients compared with 63% in 19 ADHD comorbid with TD, OCD, or TS patients, with the method of immunofluorescence. None of the nc-ADHD had both ASO and anti-DNAseB titer elevations compared with 22% of comorbid ADHD cases. The different rate of ABGA positivity of Kiessling et al. [35] study and Aguilera et al. [13] study could be explained because of the different methodology used to measure ABGA.
More recently, Toto et al. [12] studied the presence of ABGA in 20 nc-ADHD patients. They found 30% of ABGA positivity in nc-ADHD participants compared with 5% of controls, with the method by Church et al. [36]. Of these patients with positive ABGA, 50% also had high titers of ASO compared with 15% of controls, but they did not study anti-DNAseB titers. In Aguilera et al. [13] matched groups, two anti-streptococcal titer elevations were not significantly different between ADHD patients and controls. In other studies, ABGA is usually associated to GAS infection [36, 37].
The different ABGA positivity of Toto et al. [12] study could be explained by the fact that their ADHD group had more frequent ASO elevations. This could indicate that the group with ADHD had more streptococcal infections. However, given the fact that the groups were not matched by season of sample collection, it is not possible to know whether streptococcal infections and therefore ABGA positivity were related to ADHD, or to the presence of an outburst of GAS infections. 
Aguilera et al. [13] did not find more evidence of GAS infections in their ADHD group by detecting elevations of two different antibodies and checking the presence of GAS in the throat. However, the dynamic nature of GAS must be taken into consideration in the design, especially when samples are collected at a single point in time. In this regard, they had one limitation because their institution is a referral national center, and they did not control geographical variation of GAS outbursts. To overcome this limitation, they compared 20 patients and 20 controls recruited from the same urban area in the same season. Still, they did not find more evidence of GAS infections. In addition, past history did not suggest that unspecific or documented GAS infections were more frequent in ADHD patients than in controls.
ADHD is defined as a chronic condition, with a complex gene–environment interaction implied in the etiopathogenesis. Estimated heritability rates are about 60% to 75% but several risk pathways may contribute to a similar phenotype [38]. Apart from inherited and non-inherited genetic factors, the most reliable contributors described in ADHD include low birth weight, prematurity, and severe early social adversity, each one present in some participants [39]. Most of them are risk factors that may interfere with early development of neural networks involved in ADHD [40].
ADHD seems to be the common end of diverse risk pathways, as it is represented in the non-selected sample. The theory of complex gene–environmental interactions in neuro-developmental disorders, such as TS or TOC, is supported in some cases by the evidence of the role of autoimmunity as an environmental contributing factor [41]. However, autoimmunity related to GAS does not seem to play a role in nc-ADHD, when Aguilera et al. [13] results are considered. 
Inconsistent results have been obtained also in other neurodevelopmental disorders, where the use of different methodologies appears to yield results in contrast to neuroimmunological findings [42]. This should encourage the search for more sophisticated etiopathogenetic models, which can capture the complexity of the clinical presentations of neurodevelopmental disorders [43].
The ADHD phenotype currently accepted in international classifications is in most cases different from that described in PANDAS, in which clinical deterioration typically occurs overnight and rapid improvement is observed after antibiotic treatment [44]. Moreover, ADHD according to DSM-IV diagnosis is also different from what has been described in autoantibody-associated central nervous system disorders, in which onset is acute or subacute, and is followed by a slower evolution with a remission of the symptoms over weeks after treatment [45].
Searching for ABGA and evidence of GAS infection in ADHD has found conflicting results [12], and Aguilera et al. [13] case-control study, with a detailed methodology to differentiate patients and healthy controls, has contributed with negative findings. Some evidence of a temporal relationship was reported in a study of 693 schoolchildren, in which data on GAS infection and ADHD behavioural measures were collected monthly over 8 months."