Twenty children sequentially admitted to the paediatric ward, Tauranga Hospital, with a diagnosis of acute glomerulonephritis, are reviewed for evidence of recent streptococcal infection as at admission. Sixteen children (80 percent) were shown to have at least one streptococcal antibody titre (ASO and anti-DNase B) elevated above the upper limit of normal for the population. Two children had negligible antibody levels detected. Case histories and/or cultural results provided additional supportive evidence for recent streptococcal infection. Serotypes of recognised nephritogenic potential were isolated from five patients.

Evidence is presented for the probable association of streptococcal skin infection (M type 57) with six cases of acute glomerulonephritis. M type 57 streptococcus was isolated from skin infections in four of the cases and from skin sores occurring in sibling contacts of the other two. Two of the cases occurred at a time when M type 57 streptococcus predominated in skin lesions of children from the same school. A further two cases of post-streptococcal nephritis with possible involvement of M type 57 are discussed. The superiority of the anti-DNase B test over anti-streptolysin O determination in a situation when streptococcal pyoderma nephritis has occurred is shown.

Prinqual, a new statistical data-analysis method was used to determine the critical titers of antistreptolysin O (ASLO), anti-DNase B (ADB) and antistreptokinase (ASK) in the sera of 104 patients with suspected streptococcal infection and 121 blood-donors. The whole range from pathological to normal was thus covered, thereby avoiding bias concerning the proportion of normal titers in a control population. Another advantage of the method was that the titers of the 3 antibodies were considered simultaneously and the semi-quantitative results of serological tests were avoided. It appeared from this study that the upper limits of normal values were: ASLO, 100 U; ADB, 240 U and ASK, 40 U. The first probably pathological values were: ASLO, 150 U; ADB, 480 U and ASK, 320 U. These results are compared with those available in the literature.

OBJECTIVE

To evaluate the diagnostic value of streptococcal serology in adult early arthritis patients in discriminating between post-streptococcal reactive arthritis (PSRA) and arthritis with other causes.

METHODS

The antistreptolysin-O (ASO) and anti-DNase B tests were performed at baseline in 366 consecutive, newly referred early arthritis patients. After 1 yr of follow-up the patients were classified according to international classification criteria and were evaluated for the presence of persistent arthritis. The outcome measures were the predictive value of streptococcal serology for the diagnosis of PSRA and the ability of this serology to discriminate at the first visit between the self-limiting and persistent forms of arthritis.

RESULTS

With a positive serological result, the probability of having PSRA increased from 2 to 9%, whereas the probabilities of having rheumatoid arthritis or undifferentiated arthritis continued to be high (23 and 29%). The serological tests did not discriminate between the self-limiting and persistent forms of arthritis. The major Jones criteria apart from arthritis were not observed.

CONCLUSIONS

Streptococcal serology has no diagnostic value in adult early arthritis patients in whom major Jones criteria other than arthritis are not present.

Current diagnosis of Acute Rheumatic Fever and Rheumatic Heart Disease (ARF/RHD) relies on a battery of clinical observations aided by technologically advanced diagnostic tools and non-specific laboratory tests. The laboratory-based assays fall into two categories: those that (1) detect "evidence of preceding streptococcal infections" (ASOT, anti-DNAse B, isolation of the Group A Streptococcus from a throat swab) and (2) those that detect an ongoing inflammatory process (ESR and CRP). These laboratory tests are positive during any streptococcal infection and are non-specific for the diagnosis of ARF/RHD. Over the last few decades, we have accumulated considerable knowledge about streptococcal biology and the immunopathological mechanisms that contribute to the development, progression and exacerbation of ARF/RHD. Although our knowledge is incomplete and many more years will be devoted to understanding the exact molecular and cellular mechanisms involved in the spectrum of clinical manifestations of ARF/RHD, in this commentary we contend that there is sufficient understanding of the disease process that using currently available technologies it is possible to identify pathogen associated peptides and develop a specific test for ARF/RHD. It is our view that with collaboration and sharing of well-characterised serial blood samples from patients with ARF/RHD from different regions, antibody array technology and/or T-cell tetramers could be used to identify streptococcal peptides specific to ARF/RHD. The availability of an appropriate animal model for this uniquely human disease can further facilitate the determination as to whether these peptides are pathognomonic. Identification of such peptides will also facilitate testing of potential anti-streptococcal vaccines for safety and avoid potential candidates that may pre-dispose potential vaccine recipients to adverse outcomes. Such peptides can also be readily incorporated into a universally affordable point of care device for both primary and tertiary care.

Keywords: M protein; diagnostic test (MeSH); group A streptococcus; rheumatic fever; rheumatic heart disease.

Down-regulation of the signal transducer and activity of transcription 3 (Stat3) plays a crucial role in suppression of many solid tumors. Intratumoral injection of a gene carrier applying Stat3-small hairpin RNA (St3-shRNA) is a potential therapeutic strategy. To our knowledge, this is the first report of the intratumoral injection of St3-shRNA using a gene carrier. We herein designed biodegradable (methoxy)polyethylene glycol-b-(polycaprolactone-ran-polylactide) copolymer (MP) derivatized with a spermine group with cationic properties at the pendant position of the MP chain (MP-NH2). The designed MP-NH2 can act as a gene carrier of St3-shRNA by forming an electrostatic complex with cationic spermine. This can increase the stability of the complexes because of protection of PEG in biologic environments and can exhibit a sol-gel phase transition around body temperature for the formation of intratumorally injected MP-NH2 hydrogel depot for St3-shRNA. MP-NH2 was observed to completely condense with St3-shRNA to form St3-shRNA/MP-NH2 complexes. These complexes were protected for a relatively long time (≥72 h) from external biologic molecules of the serum, DNase, and heparin. St3-shRNA/MP-NH2 complexes in in vitro tumor cell experiments can enhance transfection of St3-shRNA, correspondingly enhance Stat3 knockdown efficiency, and inhibit tumor cell growth. St3-shRNA/MP-NH2 complexes and St3-shRNA/MP-NH2 complex-loaded hydrogel were intratumorally injected into the tumor as new efficient delivery carriers and depots of St3-shRNA. The intratumoral injection of St3-shRNA/MP-NH2 complexes and St3-shRNA/MP-NH2 complex-loaded hydrogel showed effective anti-tumor effect for an extended period of time due to the effect of Stat3 knockdown. Collectively, the development of MP-NH2 as a carrier and depot of St3-shRNA provides a new strategy for St3-shRNA therapy through intratumoral injection with high efficacy and minimal adverse effects.

Deoxyribonuclease I (DNase I) binds right-handed DNA duplex via a minor groove and the backbone phosphate group with no contact to the major groove. It hydrolyses double-stranded DNA predominantly by a single-stranded nicking mechanism under physiological conditions, in the presence of divalent Mg and Ca cations. Even though DNase-RNA interaction was observed, less is known about the protein-RNA binding mode and the effect of such complexation on both protein and RNA conformations. The aim of this study was to examine the effects of DNase I-tRNA interaction on tRNA and protein conformations. The interaction of DNase I with tRNA is monitored under physiological conditions, in the absence of Mg2+, using constant DNA concentration of 12.5 mM (phosphate) and various protein contents (10 microM to 250 microM). FTIR, UV-visible, and CD spectroscopic methods were used to analyze the protein binding mode, the binding constant, and the effects of polynucleotide-enzyme interaction on both tRNA and protein conformations. Spectroscopic evidence showed major DNase-PO2 and minor groove interactions with overall binding constant of K = 2.1 (+/-0.7) x 10(4) M(-1). The DNase I-tRNA interaction alters protein secondary structure with major reduction of the alpha-helix, and increases the random coil, beta-anti and turn structures, while tRNA remains in the A-conformation. No digestion of tRNA by DNase I was observed in the protein-tRNA complexes.

Acute rheumatic fever in an adult is a rare entity. We present a 29-year-old man of mixed ancestry, including Native Hawaiian and other Pacific Islander, who presented with a 6-week history of migratory polyarthralgia and fever with a recent history of purulent lower extremity wounds and a remote history of acute rheumatic fever in childhood. The diagnosis of recurrent acute rheumatic fever was confirmed by elevated Antistreptolysin-O titers and Anti-DNase B titers. This case presentation showcases a Native Hawaiian and other Pacific Islander with acute rheumatic fever in both childhood and adulthood following pyoderma infection, with a delay in diagnosis and management for both episodes. The patient had an excellent response to naproxen without developing complications and was restarted on secondary antibiotic prophylaxis. Health care providers in the Pacific region should understand the relationship between pyoderma and acute rheumatic fever in addition to including acute rheumatic fever in the differential diagnosis of polyarthralgia in an adult.

A microhaemagglutination test in disposable U plates has been devised for rapid, quantitative evaluation in antistreptococcal antibodies in human sera. Fresh or freeze-dried glutaraldehyde-treated sheep erythrocytes sensitized with over fifteen extracellular proteins released by group A Streptococcus pyogenes including streptolysin O, deoxyribonucleases, hyaluronatelyase, streptokinase and nicotinamide dinucleotide glycohydrolase were used. Haemagglutination and anti-streptolysin O (ASLO) titers were determined in parallel on 434 serum specimens from 123 healthy subjects ("controls") and 311 patients with a history of supposed or evident streptococcal infection. The titration of the four above-mentioned anti-enzyme antibodies has also been made on about 100 sera from both groups. Haemagglutination titre (HT) was less than 800 in control sera. By contrast it was greater than 800 up to 12 800 in patients specimens. Very good correlation was found between HT on the one hand and ASLO or anti-SK, anti-HA and anti-NADase antibodies on the other hand. HT and anti-DNase B antibodies were less correlated. Haemagglutination titres appear to rise earlier than serological titres of conventional streptococcal antibodies. The haemagglutination test described may be particularly helpful as a rapid serologic indicator of streptococcal infections and more reliable than the titration of ASLO alone, or of any one of anti-enzyme antibodies.

OBJECTIVE

We studied a case of acute posterior multifocal placoid pigment epitheliopathy in a 40-year-old man who had had an acute febrile illness.

METHODS

The medical record was reviewed for clinical manifestations, course of disease, and laboratory findings, including results of fluorescein and indocyanine green angiography.

RESULTS

The patient had the typical clinical course of acute posterior multifocal placoid pigment epitheliopathy with spontaneous resolution of posterior pole lesions and improvement in visual acuity from 20/60 to 20/20. The laboratory evaluation was remarkable for a rise in the anti-DNAse B antibody titer between initial and convalescent-phase serum samples, providing evidence of recent group A streptococcal infection.

CONCLUSIONS

Although acute posterior multifocal placoid pigment epitheliopathy is often attributed to a postviral condition, this syndrome may also develop after an acute group A streptococcal infection.

OBJECTIVE

A concurrent group A beta-hemolytic Streptococcus (GABHS)-influenza virus pharyngotonsillitis (PT) is generally not considered in diagnoses, even though mixed bacterial-viral infections are common in other respiratory tract infections. This report describes our experience in diagnosing a potential mixed GABHS-influenza virus PT in children.

METHODS

Acute and convalescent antistreptolysin O (ASO) and anti-DNase B titers were obtained from 12 children with acute PT and clinical presentation that suggested viral infection, and in whom both rapid influenza A virus and rapid GABHS tests were positive.

RESULTS

The children did not receive any antimicrobial therapy, and all recovered from their acute PT within 2 to 5 days and were all asymptomatic upon their return visit 3 to 4 weeks later. GABHS was recovered from 2 of the children on their return visit. However, ASO and anti-DNase B titers were not elevated in these individuals. The ASO and anti-DNase B titers determined in the first serum samples were less than the age-adjusted normal values for all of the children. However, these titers rose by at least two-dilution (0.2 logarithm) in the convalescent sera as compared with the acute ones in 4 of the 12 children (33%). One of the 8 children who had no increase in ASO and anti-DNase B titers had an acute GABHS PT 5 months later. One-year follow-up of all of the children showed no anomalies.

CONCLUSIONS

This report is the first to describe a concomitant GABHS and influenza A virus PT, as evident by increased ASO and anti-DNase B titers in a third of the patients who had both of these organisms detected in their upper airways.

The nuclease activity of deoxyribonuclease 1 (DNase I) is regulated by alternative splicing (AS) of its mRNA. The aim of this study was to define the ability of a splice-switching oligonucleotide (SSO) that base-paired with DNase I pre-mRNA to induce AS and inhibit nuclease activity in human T, B and NK lymphocytes. The SSO for DNase I could significantly downregulate the expression of full-length active DNase I and upregulate a truncated splice variant with a deleted exon 4. Such an induction of AS resulted in inhibition of nuclease activity and slowed apoptosis progression in anti-CD95/FAS stimulated lymphocytes. These results should facilitate further investigations of apoptosis regulation in lymphocytes and demonstrate that SSOs for DNase I are promising cytoprotective agents.

OBJECTIVE

To determine whether centromeric CENP A, B and C proteins play a role in centromere survival.

METHODS

Sixteen anti-centromere sera from scleroderma patients were used. The most common reactivity demonstrated by Western blot was anti-CENP-A, followed by anti-CENP-B and -C, in that order. The reactivity of these sera with HEp-2 cells was studied using an indirect immunofluorescence assay with and without prior digestion by a DNase, Aspergillus nuclease and the restriction endonucleases Bam HI, Hind III, and Eco RI. CENP-B was purified using affinity chromatography and anti-CENP-B antibody. The interaction between CENP-B and the CENP-B box was evaluated using immunoprecipitation. Precipitates containing alphaDNA were amplified using a PCR method with specific primers for the CENP-B box.

RESULTS

None of the nucleases altered the fluorescence pattern. PCR amplification showed that CENP-B adsorbed on a Sepharose-4B/anti-CENP-B antibody column retained alphaDNA satellites. No retention was seen in the absence of CENP-B.

CONCLUSIONS

CENP-B protects alphaDNA from digestion by nucleases and prevents DNase or restriction enzyme digestion from affecting the morphology and location of centromeres. CENP-B may promote and maintain joining of DNA satellites in the centromere.

OBJECTIVE

To report the pharyngeal colonization rate of β-hemolytic streptococci and changes in the value of antistreptolysin O (ASO) and anti-DNase B serology titers during pregnancy.

METHODS

Healthy pregnant women were recruited and blood was drawn in each trimester. The upper limit of normal (ULN) values for ASO and anti-DNase B was calculated for each trimester. Throat swabs were collected for culture and positive cultures were further assessed for the identification of serogroup of the isolated β-hemolytic streptococcus.

RESULTS

Out of a total of 126 pregnant women, 34.1% had positive throat cultures. Group C and group G strains were isolated in 18.2% of throat cultures while group F was detected in 13.5% of cases. The rate of colonization with GAS was 1.6%. There was an overall drop in ASO titer during pregnancy while anti-DNase B titers remained relatively unchanged. ULN values of 164(IU), 157(IU), and 156(IU) were calculated for ASO at the first, second, and third trimesters, respectively. Based on the ULN values, 28.6% of patients had recent streptococcal exposure.

CONCLUSIONS

These results show that pregnant women act as a reservoir for spreading potentially immunogenic (groups C and G) and disease producing (group F) virulent strains of streptococci.

The antidesoxyribonuclease B reaction shows in persons of all classes of age examined a similar distribution of titres as the antistreptolysin reaction. The anti DNase B titres however are mostly lower than the titres of the antistreptolysin reaction, except in the group of children, 6 to 17 years of age, suffering frequently from latent infections of streptococci. Women in childbed showed lower anti DNase B titres than other persons of corresponding age. Among persons with anti DNase B titres higher than antistreptolysin titres predominate men.

Antibodies to streptococcal Estreptolysin O and DNAse B were sampled from 1986 through 1989 in 135 healthy individuals of both sexes, grouped by age, at a metropolitan area of Santiago, Chile, and their geometric mean titers (GMT) were calculated. GMT of 110 U (Todd) for Antiestreptolysin and 194 U for Anti-DNAse B were recorded in the whole sample. Antiestreptolysin O titers were 62 UT for age group 5 to 9 years, 127 UT for 10 to 14 year olds and 114 UT for ages 15 or older. Anti-DNAse B titers for the same age groups were 158 U, 240 U and 198 U respectively. No significant differences were detected between these results and those from an earlier (1978 to 1981) study, except for Anti-DNase B titers in 5 to 9 years olds, which were significantly lower (GMT 158 U vs. 270 U) in the most recent screening.

A colorimetric method for measuring anti-NAD+ glycohydrolase in human sera has been developed. The assay involves the inhibition of NAD+ glycohydrolase (EC 3.2.2.5) by the antibody and determination of the noninhibited enzyme activity by using an enzymatic amplifying system for NAD+. The assay is easily carried out and has the additional advantage of a direct relationship between signal and antibody concentration. The results obtained for 100 human sera compare favorably with other tests commonly used to obtain evidence of streptococcal infections or their complications, such as the anti-streptolysin O and the anti-DNase B tests.

Cre-mediated cassette exchange has been developed to perform site-specific chromosomal integration using Cre recombinase. Here, site-specific integration with inverted Lox sites was used to investigate the erythroid cis-acting DNA element in specific chromatin contexts in mouse erythroleukemia cells. Single hygromycin-resistant clones were obtained from the selective semi-solid medium containing hygromycin post-electroporation. PCR and Southern blotting analysis showed single-copy integration of target vector in clones A, B and D. Site-specific cassette exchange was performed in clone A with exchange vector and Cre expression plasmid, followed by gancyclovir selection. Flow cytometry was used for analysis of EGFP gene expression. A 732-bp fragment of human beta-globin gene cluster 5' DNase I hypersensitive site 2 (HS2) was exchanged and integrated into clone A in an anti-genomic orientation. The low EGFP expression in clone A-HS may be due to the orientation-dependent gene silencing caused by integration of HS2 in a non-permissive orientation.

Rheumatic pneumonia is a pulmonary complication of rheumatic fever, often with grave outcomes. It has been described sporadically in literature, most recently a decade ago. Here, we describe a case of a 12-year-old Native American girl presenting with chest pain, gastrointestinal complaints, and frequent nosebleeds. After the initial diagnosis with acute pericarditis, she was found to meet diagnostic criteria for rheumatic fever. Revised Jones criteria met included significantly elevated streptolysin O antibody and anti-DNase B, carditis, arthralgia, fever, and elevated inflammatory markers. Findings complicating the diagnosis were an elevated antinuclear antigen with a family history of systemic lupus erythematosus (SLE), hemoptysis, and a chest CT finding of right lower lobe alveolar hemorrhage as well as right-sided mediastinal adenopathy. The patient was discharged on day nine of admission after a course of high-dose methylprednisolone with prednisone taper, furosemide, enalapril, naproxen, monthly penicillin G injections, and multidisciplinary outpatient follow-up. A repeat chest CT scan three months later showed significant improvement. The pulmonary findings described in our patient are consistent with prior reports of rheumatic pneumonia, however, most prior cases described did not include high-resolution imaging. Our patient recovered well aside from complications secondary to mitral regurgitation, unlike many patients seen in our literature search who died due to early or later complications of pulmonary disease. Although acute rheumatic fever, and its pulmonary complications, is significantly less common than it once was, it remains a disease entity that should remain on the differential for multisystem rheumatic complaints.

Autoantibodies characteristic for anti-phospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti-β2 -glycoprotein I (β2 GPI) antibodies and anti-DNA antibodies, respectively, and almost half of APS cases occur in SLE. Anti-β2 GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely accepted view, binding of anti-β2 GPI antibodies to cell surface β2 GPI in monocytes and endothelial cells triggers the Toll-like receptor 4-myeloid differentiation primary response 88 (TLR)-4-MyD88) signaling pathway which leads to activation of p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinases (MEK-1/ERK) and/or nuclear factor kappa B (NF-κB) and expression of tissue factor (TF). However, resting cells do not express substantial amounts of TLR-4. Previously, we generated a mouse monoclonal anti-β2 GPI antibody WB-6 and showed that it induced a prothrombotic state - including TF expression on circulating monocytes - in normal mice. In the current study, we aimed to clarify the mechanism of interaction between WB-6 and resting monocytes, and found that WB-6 exhibits binding activity to DNA and enters living monocytes or a monocytic cell line and, to a lesser extent, vascular endothelial cells. Treatment of the cells with DNase I reduced the internalization, suggesting the involvement of cell surface DNA in this phenomenon. Monocytes harboring internalized WB-6 expressed TF and tumor necrosis factor (TNF)-α which, in turn, stimulated endothelial cells to express intercellular adhesion molecule 1 (ICAM-I) and vascular cell adhesion molecule 1 (VCAM-I). These results suggest the possibility that a subset of anti-β2 GPI antibodies with dual reactivity to DNA possesses ability to stimulate DNA sensors in the cytoplasm, in addition to the cell surface receptor-mediated pathways, leading to produce proinflammatory and prothrombotic states.

The mechanism(s) of anti-DNA antibody formation was comparatively investigated using in vitro human and murine B-cell culture systems. T-cell homogenate (TH) from SLE patients converted normal human B-cells to anti-DNA specific antibody-forming plasma cells (anti-DNA-SPC) when cultured with calf thymic native DNA as antigen. TH of normal human donors suppressed the formation of anti-DNA-SPC from normal human B-cell cultures even when SLE TH and DNA were added to the cultures. B-cells derived from SLE patients were insensitive to normal human TH, and resulted in the formation of many anti-DNA-SPC. TH of young and old NZB mice stimulated the formation of anti-DNA-SPC from not only NZB but also C57BL/6 murine bone marrow cultures in the presence of DNA antigen. Human and murine TH, and both B-cell cultures were reciprocally combined to test whether xenogeneic TH stimulated B-cell cultures from different species. Xenogeneic TH was effective in triggering differentiation of xenogeneic B-cells with respect to anti-DNA-SPC. The elimination of helper T-subsets (Th) resulted in the generation of fewer anti-DNA-SPC, whereas the elimination of suppressor T-subsets (Ts) caused the formation of many anti-DNA-SPC. Among organ homogenates, e.g., liver, kidney and, brain, and T-cells from old NZB mice, TH was most effective in the stimulation of anti-DNA-SPC. The effective substance was sensitive to RNase-A, but resistant to pronase and DNase-I. Phenol extracted T-cell RNA retained its activity. We concluded that the functional modulation of helper T-cells, which reflects RNA molecules, could be the main etiology of autoantibody formation against DNA by both human and murine B-cells.

The purpose of this study was to reveal the presence of Z-helical conformation in normal crystalline lens DNA. Z-DNA antigen was prepared against poly(dG-dC).poly(dG-dC), which had been converted to the Z-helix conformation in high salt and then stabilized by bromination. Circular dichroism (CD) spectra confirmed the presence of left-handed Z-helix DNA. Antibodies to Z-DNA were raised in three rabbits immunized with brominated (Br-) poly(dG-dC).poly(dG-dC). These antibodies do not cross-react with polynucleotides in the B-helical form, but are specific to the left-handed Z-DNA conformation. DNA was isolated from three different regions of the calf lens. Anti-Z-DNA antisera, affinity purified IgG polyclonal anti-Z-DNA antibodies and monoclonal anti-Z-DNA antibodies were used as immunoprobes to detect the presence of S-DNA sequences. DNA from the cortex region of the lens reacted strongly with the anti-Z-DNA antibodies, but no binding could be observed in the DNA from the nucleus region. Digestion of lens DNA with DNase 1 dramatically decreased Z-DNA antibody binding, while RNase A and T1 treatment had no effect on Z-DNA immunoreactivity. This study has demonstrated that: (a) Z-DNA antibodies developed for our study can bind in high salt solutions (4M NaCl) to purified lens DNA sequences isolated from a variety of different calf lens cell types. By this criterion, lens DNA contains sequence determinants which may assume or are in the Z-helix conformation.

Background: To explore the relationship between adult Attention Deficit/ Hyperactivity Disorder (ADHD), antistreptococcal titers, ABGA, and recurrent infections during early childhood.

Method: Childhood history of recurrent infections and a blood sample were collected in a sample of DSM-IV adult outpatients with ADHD. The anti-streptolysin O (ASO), anti-deoxyribonuclease B (anti-DNase B), and anti-basal ganglia antibodies (ABGA) titers were determined in patient plasma by enzyme-linked immunosorbent assay (ELISA). Titers positivity was evaluated following manufacturer's specifications. Absolute titers were also collected as continuous variables.

Results: Fourteen out of 22 (63.6%) have had recurrent infections in childhood (i.e., seven, 31.8%, have had tonsillitis or adenoiditis and seven, 31.8%, have had any other infections). Eighteen patients (81.9%) were positive for anti-DNase B, five (22.7%) for ASO, and 4 (18.2%) were positive for both of them. Five participants (22.7%) were ABGA positive, whereas only two (9.1%) were positive for all three antibodies.

Conclusions: patients with ADHD might be more prone to infections during childhood and subclinical streptococcal infections during adulthood. Moreover, they seem to have an increased risk for basal ganglia autoimmunity in adulthood. Both infections and the ensuing acquired autoimmunity could influence the neurodevelopmental process, by contributing, at least in part, to the ADHD pathogenesis.

Keywords: ABGA; ADHD; Adult; Anti-deoxyribonuclease B; Anti-streptolysin O; Basal ganglia; Group a streptococcus.