X-linked congenital adrenal hypoplasia: Report of long clinical follow-up and description of a new complex variant in the NR0B1 gene.

Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.

Prenatal Findings in Postnatal Cases of Disorders of Sex Development: Experience from a Tertiary-Specialized Center in Brazil.

INTRODUCTION AND OBJECTIVE: Prenatal suspicion of disorders/differences of sex development (DSDs) is a relatively new phenomenon. The aim of this study was to review the prenatal findings of DSD cases postnatally diagnosed in our tertiary referral center. METHODS: We evaluated 57 DSD cases with sex ambiguity who had undergone prenatal ultrasound with phenotypic sex assessment and/or cell-free fetal DNA (cffDNA) for genotypic sex assessment. RESULTS: Prenatal cffDNA had been performed in 32 cases, being positive (suggestive of male genotypic sex) in 26 and negative (suggestive of female genotypic sex) in 6. Five with cffDNA negative had a prenatal ultrasound indicating female external genitalia, in turn, in those with cffDNA positive, only two had a prenatal ultrasound indicating male external genitalia. Our postnatal data showed that when external genitalia were female or poorly virilized, prenatal ultrasound indicated female sex, but in cases of higher degree of virilization, ultrasound showed similar rates of male, female, or undetermined sex. Regarding the karyotype, our data showed those with XY karyotype had positive cffDNA, those with XX karyotype had negative cffDNA, and all five with sex chromosome anomalies had positive cffDNA because they were 45,X/46,XY. We suggested an algorithm to investigate these cases during gestation, including evaluation of uterus, fetal growth, and malformations. CONCLUSION: We suggest that the parents should be counseled prenatally by a dedicated multidisciplinary team with experience in DSD management and evaluated as soon as possible after birth.

Homogeneity in Motor Competence Among Youths With Intellectual Disability With and Without Down Syndrome.

PURPOSE: To determine if there is a homogeneity of scores for youth with intellectual disability (ID) with and without Down syndrome (DS) in 19 test items of motor competence from the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2). Homogeneity was defined as the means for each of the 19 test items scores by sex and the presence or absence of DS sharing the same population mean. METHOD: Participants were 622 youth with ID aged 6 to 21 years. Items for bilateral coordination, balance, and upper limb coordination were examined using the BOT-2. RESULTS: For all 19 BOT-2 items, means between youth with and without DS did not differ from the population mean. CONCLUSION: These results potentiate the development of expected BOT-2 motor competence scores for youth with ID independent of the presence of DS for clinical practice.

SOX3 duplication in a boy with 46,XX ovotesticular disorder of sex development and his 46,XX sister with atypical genitalia: Probable germline mosaicism.

Ovotesticular disorders of sex development (OT-DSD) are characterized by ovarian follicles and seminiferous tubules in the same individual, with a wide range of atypical genitalia. We report on two sibs with atypical genitalia and SRY-negative 46,XX DSD, OT-DSD was confirmed only in the boy, while the girl had bilateral ovaries. Chromosome microarray analysis (CMA) showed a 737-kb duplication at Xq27.1 including the entire SOX3 gene in both sibs, which was confirmed by quantitative real time PCR. Also, X chromosome inactivation assay showed random inactivation in both sibs. Whole exome sequencing revealed no pathogenic or likely pathogenic variant. CMA of the parents showed normal results for both, suggesting that germline mosaicism could be the reason of recurrence of this duplication in the siblings. Our results support a pathogenic role of SOX3 overexpression in 46,XX subjects leading to variable DSD phenotypes.

Leptin's Immune Action: A Review Beyond Satiety.

The adipose tissue is an endocrine organ that secretes adipokines such as leptin, which is one of the most important hormones for controlling satiety, metabolism, and energy homeostasis. This hormone acts in the regulation of innate and adaptive immune responses since immune cells have leptin receptors from which this hormone initiates its biological action. These receptors have been identified in hematopoietic stem cells in the bone marrow and mature immune cells, inducing signaling pathways mediated by JAK/STAT, PI3K, and ERK 1/2. It is known that the bone marrow also contains leptin-producing adipocytes, which are crucial for regulating hematopoiesis through largely unknown mechanisms. Therefore, we have reviewed the roles of leptin inside and outside the bone marrow, going beyond its action in the control of satiety.

Growth, puberty and testicular function in boys born small for gestational age with a nonspecific disorder of sex development.

OBJECTIVE: Being born small for gestational age (SGA) is frequently associated with unexplained disorders of sex development (nonspecific DSD) in boys. Little is known about their future growth, puberty and testicular function. Our objective is to determine the long-term endocrine outcome of boys born SGA who have a nonspecific DSD. DESIGN: Boys with a nonspecific DSD born SGA and appropriate for GA (AGA) were retrieved through the International Disorders of Sex Development registry and retrospective data collected, based on a spreadsheet containing 102 items. PATIENTS AND MEASUREMENTS: In total, 179 boys were included, of which 115 were born SGA and 64 were born AGA. Their growth and pubertal development were compared. Serum LH, FSH, testosterone, AMH and inhibin B levels in infancy and puberty were analysed to assess testicular function. RESULTS: At 2 years of age, 30% of SGA boys had incomplete or absent catch-up growth. Boys born SGA also had higher LH during minipuberty and lower testosterone in stimulation tests (p = 0.037 and 0.040, respectively), as compared to boys born AGA. No differences were observed in timing or course of puberty or end-pubertal hormone levels. CONCLUSIONS: Almost one out of three SGA boys with a nonspecific DSD experiences insufficient catch-up growth. In addition, our data suggest dysfunction of infantile Leydig cells or altered regulation of the hypothalamic-pituitary-gonadal axis in SGA boys during childhood. Sex steroid production during puberty seems unaffected.

Normal bone health in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy.

It is of great importance to investigate any potential detrimental effect on bone health in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy. This study demonstrated normal bone health in well-controlled patients. Additionally, glucocorticoid dose may play an important role in the mineral density of femoral neck region. PURPOSE: To compare regional bone mineral densities (BMDs) and bone statuses of young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency with a control group. The duration and dose of glucocorticoid therapy and relative skeletal muscle index (an indicator of sarcopenia) were also analyzed as parameters to predict bone health. METHODS: This case-control study included 23 patients (7 male and 16 female) and 20 controls (8 male and 12 female) matched by age range (18 to 31 years). Dual energy X-ray absorptiometry and phalangeal quantitative ultrasound (QUS) were used to estimate BMD and bone status, respectively. RESULTS: No difference was observed between patients and controls (of both sexes) in absolute values of BMD and Z-scores for the total body, lumbar spine, and femoral neck; or the bone status (estimated by phalangeal QUS). Multiple linear regression analysis demonstrated that relative skeletal muscle index independently correlated with BMD of the entire body (ß: 0.67, P = 0.007), the lumbar spine (ß: 0.73, P = 0.005), and the femoral neck (ß: 0.67, P = 0.007). However, the dose of glucocorticoids (ß: - 0.38, P = 0.028) independently correlated with BMD in the femoral neck region alone. CONCLUSION: No signs of change in bone health were observed in patients with CAH when compared to the reference group. Additionally, a marker of sarcopenia was demonstrated to have a role in mineral density mechanisms in all analyzed bone sites. Only the femoral neck BMD seemed to be significantly dependent on glucocorticoid dose.

A Novel Look at Dosage-Sensitive Sex Locus Xp21.2 in a Case of 46,XY Partial Gonadal Dysgenesis without NR0B1 Duplication.

A region of 160 kb at Xp21.2 has been defined as dosage-sensitive sex reversal (DSS) and includes the NR0B1 gene, considered to be the candidate gene involved in XY gonadal dysgenesis if overexpressed. We describe a girl with 46,XY partial gonadal dysgenesis carrying a 297 kb duplication at Xp21.2 upstream of NR0B1 initially detected by chromosomal microarray analysis. Fine mapping of the breakpoints by whole-genome sequencing showed a tandem duplication of TASL (CXorf21), GK and partially TAB3, upstream of NR0B1. This is the first description of an Xp21.2 duplication upstream of NR0B1 associated with 46,XY partial gonadal dysgenesis.

Cardiovascular dysfunction risk in young adults with congenital adrenal hyperplasia caused by 21-hydroxylase enzyme deficiency.

BACKGROUND: The association of congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase enzyme (21OHase) deficiency, duration of treatment and dosage with cardiovascular dysfunction in young adults remains unclear. We aimed to evaluate myocardial function, vascular structures and epicardial fat thickness in young adults with CAH as a result of 21OHase deficiency. Correlations between the duration and dose of glucocorticoid therapy and cardiovascular parameters were analysed. METHODS: This case-control study of young adults (18-31 years old) included 20 patients (5 men and 15 women) and 16 control subjects (8 men and 8 women). Echocardiographic analysis was performed using high-resolution ultrasound. RESULTS: No ultrasonographic changes in any indices of myocardial function, vascular structures and epicardial fat thickness were found in patients, except for an impaired left ventricular end-diastolic diameter in female patients (28.1 ± 1.6 vs 26.0 ± 2.4 mm/m2 , P = .021), compared with those in individuals in the control group. Nevertheless, the individual patient values were within the normal range. Multiple linear regression analysis in female patients demonstrated that an elevated daily dose of glucocorticoids correlated with increased indices of left ventricular posterior wall thickness (Partial r = 0.68, P = .007), left ventricular end-diastolic diameter (Partial r = 0.62, P = .017), aortic diameter (Partial r = 0.60, P = .022) and left carotid artery intima-media thickness (Partial r = 0.61, P = .021), independently of treatment duration. CONCLUSION: No signs of cardiovascular dysfunction were observed in any patient. The daily dose of glucocorticoids may play a role in the mechanisms of some markers of cardiac hypertrophy, left ventricular and aortic dilation and subclinical atherosclerosis.

Mutation update for the NR5A1 gene involved in DSD and infertility.

Nuclear receptor subfamily 5 group A member 1 (NR5A1), also named steroidogenic factor 1, is an essential transcription factor that regulates a number of target genes crucial for normal reproductive physiology and endocrine function. It is encoded by NR5A1 gene and is expressed in high doses mainly in steroidogenic tissues, where it controls several steps of adrenal and gonadal development. NR5A1 mutations are associated with a wide phenotypic spectrum of disorders/differences of sex development (DSD), a group of conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. Here, we reviewed 188 NR5A1 mutations from 238 cases reported in literature so far. Additionally, we report the variations p.Ser4*, p.(Cys55Ser), p.(Met78Leu), and p.Met98Glyfs*45, which have not been annotated for NR5A1 before and were identified in some of the 205 46,XY patients of our own cohort. This is the first NR5A1 mutation review which includes both 46,XX and 46,XY karyotype, with the purpose of discussing the complexity of genotype-phenotype correlations among DSD and infertile male patients and also females with primary ovarian failure.

Promises and pitfalls of whole-exome sequencing exemplified by a nephrotic syndrome family.

High-throughput techniques such as whole-exome sequencing (WES) show promise for the identification of candidate genes that underlie Mendelian diseases such as nephrotic syndrome (NS). These techniques have enabled the identification of a proportion of the approximately 54 genes associated with NS. However, the main pitfall of using WES in clinical and research practice is the identification of multiple variants, which hampers interpretation during downstream analysis. One useful strategy is to evaluate the co-inheritance of rare variants in affected family members. Here, we performed WES of a patient with steroid-resistant NS (SRNS) and intermittent microhematuria. Currently, 15 years after kidney transplantation, this patient presents normal kidney function. The patient was found to be homozygous for a rare MYO1E stop-gain variant, and was heterozygous for rare variants in NS-associated genes, COL4A4, KANK1, LAMB2, ANLN, E2F3, and APOL1. We evaluated the presence or absence of these variants in both parents and 11 siblings, three of whom exhibited a milder phenotype of the kidney disease. Analysis of variant segregation in the family, indicated the MYO1E stop-gain variant as the putative causal variant underlying the kidney disease in the patient and two of her affected sisters. Two secondary variants in COL4A4-identified in some other affected family members-require further functional studies to determine whether they play a role in the development of microhematuria in affected family members. Our data illustrate the difficulties in distinguishing the causal pathogenic variants from incidental findings after WES-based variant analysis, especially in heterogenous genetic conditions, such as NS.

ENERGY EXPENDITURE IN 21-HYDROXYLASE CONGENITAL ADRENAL HYPERPLASIA PATIENTS AND COMPARISON WITH PREDICTIVE EQUATIONS.

Objective: To characterize resting energy expenditure (REE) in patients with classic 21-hydroxylase congenital adrenal hyperplasia (21-OH CAH) using indirect calorimetry and compare it to the most commonly used REE predictive equations. Methods: This case-control study comprised 29 post-pubertal 21-OH CAH patients regularly followed at the University of Campinas. Elevated serum 17-hydroxyprogesterone and CYP21 gene molecular analysis confirmed the diagnosis. A healthy control group paired by age, gender, and body mass index was examined. Dual-energy X-ray absorptiometry (DEXA) measured body compositions. A bioimpedance analyzer determined fat-free mass, and indirect calorimetry using a metabolic cart measured REE. Results: Unlike our initial hypothesis, REE was similar between the groups (18.7 ± 3.1 kcal/kg/day in CAH vs. 20.3 ± 3.5 kcal/kg/day in controls; P = .728). No predictive equations reached the stipulated accuracy criteria, thus lacking validity in REE assessment in adults with the characteristics of the group studied. DEXA analysis revealed higher body fat and diminished nonbone lean mass in 21-OH CAH. Anthropometric and bioelectrical impedance parameters were not significantly different. Conclusion: Classic 21-OH CAH is generally followed in reference centers, which may facilitate indirect calorimetry use for REE measurement. Alternatively, considering our REE findings in adult 21-OH CAH patients, nutrition management based on 25 kcal/body weight/day (measured REE × activity factor 1.2 to 1.3) may be reasonable for current body weight maintenance in these patients. Abbreviations: 17-OHP = 17-hydroxyprogesterone; 21-OH CAH = classic 21-hydroxylase deficiency congenital adrenal hyperplasia; BMI = body mass index; REE = resting energy expenditure; VO2 = volume of oxygen; VCO2 = volume of carbon dioxide.

Phase Angle is Determined by Body Composition and Cardiorespiratory Fitness in Adolescents.

The phase angle is used to evaluate nutritional status and is an indicator of cellular health. Cardiorespiratory fitness and body composition are strong indicators of health during adolescence. We aimed to evaluate if body composition and cardiorespiratory fitness have an association with phase angle among adolescents. 203 girls and 220 boys (12.8±1.3 years) were evaluated. Peak height velocity, percentage fat mass, fat-free mass, cardiorespiratory fitness, and phase angle measurements were collected. Linear regression adjusted by peak height velocity was used to verify if predictor variables were associated with phase angle among adolescents. Phase angle showed correlation with fat-free mass (girls: r=0.42 and boys: r=0.37); with percent fat mass (girls: r=0.23); and with cardiorespiratory fitness (boys: r=0.19). Linear regression showed that percentage fat mass (in girls) and cardiorespiratory fitness (in boys) had an effect of 11 and 17% in phase angle, respectively, while fat-free mass had an effect of 22 and 26% in phase angle for girls and boys, respectively. Changes in phase angle seem to be more associated with the percentage fat mass in girls, cardiorespiratory fitness in boys, and fat-free mass in both when controlled by peak height velocity.

Geometric indices of femur bone strength in female handball players.

The practice of sports during the growth phase has a positive influence on bone mineral accrual. However, the effects of different sports are still not fully understood. The aim of this study was to evaluate the bone geometry in adolescent handball players. This is a cross-sectional study in which 53 female adolescents (12-17 years old) were divided into two groups: handball players (HG: n = 26), who must have had at least six months of participation in official competitions, and a control group (CG: n = 27). Bone geometry properties, such as cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), and femoral strength index (FSI) were measured using DXA. Tanner's sexual maturity, menarche, peak height velocity, sun exposure, and calcium intake were assessed. An unpaired Student's t test or the Mann-Whitney test and multivariate analyzes were used to compare variables differences between groups. The HG group showed a significantly higher body mass index, weight and lean mass (LST), CSA, CSMI, Z, and FSI than the CG group. When the values were adjusted for LST, the differences disappeared. The LST has been shown to be relevant to the strength and bone stiffness of the femurs of female adolescents, and the competitive practice in handball may have contributed to its increase.

Development and Cross-Validation of a Prediction Equation for Estimating Percentage Body Fat From Body Mass Index in Young People With Intellectual Disability.

The purpose of this study was to develop and cross-validate an equation for estimating percentage body fat (%BF) from body mass index and other potential independent variables among young persons with intellectual disability. Participants were 128 persons with intellectual disability (62 women; age 16-24 years) split between development (n = 98) and cross-validation (n = 30) samples. Dual-energy X-ray absorptiometry served as the reference method for %BF. An equation including 1/body mass index and sex (0 = male; 1 = female) was highly accurate in estimating %BF (p < .001; R2 = .82; standard error of estimate = 5.22%). Mean absolute and root mean square errors were small (3.1% and 3.9%, respectively). A Bland-Altman plot indicated nearly zero mean difference between actual and predicted %BF with modest 95% confidence intervals. The prediction equation was %BF = 56.708 - (729.200 × [1/body mass index]) + (12.134 × sex). Health care professionals may use the prediction equation for monitoring %BF among young people with intellectual disability.

Comparing Motor Competence of Sex- and Age-Matched Youth With Intellectual Disability From Brazil and the United States.

Youth with intellectual disabilities (IDs) demonstrate below-criteria motor competence (MC) compared with typically developing (TD) youth. Whether differences in MC exist for youth with ID from different countries is unknown. This study examined the MC of youth with ID from Brazil (BR) and the United States (US) and compared it with norms for TD youth as established by the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2). The authors measured 19 BOT-2 test items for bilateral coordination, balance, and upper limb coordination of 502 youth (BR = 252, US = 250) with ID (6-21 years). Raw scores were converted to %ceiling (percentile of highest expected scores). For all test items, no significant differences were seen between BR and US participants in %ceiling scores. Participants from both countries demonstrated equivalent to slightly below BOT-2 norms in 14 of the 19 test items, with lowest scores seen in contralateral synchronizing bilateral coordination, balancing on one leg, and ball handling.

A group of Brazilian Turner syndrome patients: Better quality of life than the control group.

Current literature presents no consensus regarding which aspects influence health-related quality of life (HRQoL) of women with Turner syndrome (TS). The objective of the present study was to compare HRQoL in the TS and control group, using components and domains of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Observational, descriptive, and cross-sectional study with 44 women with TS aged between 18 and 30 years (TS group) and 44 healthy women of the same age which were sisters, relatives, or friends of the TS group (control group). A registration form and the SF-36 questionnaire were used to analyze HRQoL in TS in relation to the control group. The TS group presented better scores in the mental component summary and in the role physical, bodily pain, general health, social function, and role emotional domains compared to the control group. This study presented some unexpected results, different from those found in the current literature, showing the possibility of TS patients presenting better coping strategies. It is necessary to develop a specific questionnaire to assess QoL in TS and analyze in great detail which factors may influence the HRQoL of these patients.

Physical training over 6 months is associated with improved changes in phase angle, body composition, and blood glucose in healthy young males.

OBJECTIVES: The aim of this study was to evaluate the association between phase angle, body composition, and blood glucose changes in healthy young males after 6 months of physical training. METHODS: Volunteers, 98 healthy males (18.8 ± 0.5 years), had 6 months of progressive physical training (5 days a week, 90 minutes a day). Resistance, reactance, and phase angle were obtained by bioelectrical impedance analysis, body composition (fat mass, bone mineral content [BMC], and lean soft tissue [LST]) by dual-energy X-ray absorptiometry, and blood glucose by reflectance photometry. Measurements were made at rest and in a fasted state, both before and after the training period. RESULTS: Phase angle, reactance, BMC, and LST significantly increased (0.6°, 3.8 Ω, 0.1 kg, and 1.9 kg, respectively; P < .01), whereas resistance and blood glucose decreased (-11.2 Ω and -4.1 mg/dL; P < .01). Changes in resistance and reactance explained those changes observed in LST (R2 = .26 and .16, respectively), but phase angle changes were not related to body composition and blood glucose alterations (P < .05). CONCLUSIONS: A 6-month period of physical training was associated with positive changes in phase angle, body composition, and blood glucose in healthy young males, reinforcing the importance of maintaining a physically active lifestyle.

Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development.

Steroidogenic factor-1 (SF1), encoded by the NR5A1 gene, is a key regulator of steroidogenesis and reproductive development. NR5A1 mutations described in 46,XY patients with disorders of sex development (DSD) can be associated with a range of conditions of phenotypes; however, the genotype-phenotype correlation remains elusive in many cases. In the present study, we describe the impact of five NR5A1 variants (three novel: p.Arg39Cys, p.Ser32Asn, and p.Lys396Argfs*34; and two previously described: p.Cys65Tyr and p.Cys247*) on protein function, identified in seven patients with 46,XY DSD. In vitro functional analyses demonstrate that NR5A1 mutations impair protein functions and result in the DSD phenotype observed in our patients. Missense mutations in the DNA binding domain and the frameshift mutation p.Lys396Argfs*34 lead to both, markedly affected transactivation assays, and loss of DNA binding, whereas the mutation p.Cys247* retained partial transactivation capacity and the ability to bind a consensus SF1 responsive element. SF1 acts in a dose-dependent manner and regulates a cascade of genes involved in the sex determination and steroidogenesis, but in most cases reported so far, still lead to a sufficient adrenal steroidogenesis and function, just like in our cases, in which heterozygous mutations are associated to 46,XY DSD with intact adrenal steroid biosynthesis.

The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers.

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. We identified 12 unrelated families (13 patients) with typical signs of APS1 in the proband, and the screening of relatives recognized an asymptomatic child. Candidiasis was present in all cases, and 19 other manifestations were observed. All patients carried one of 10 different mutations in AIRE, being 3 new ones, and were positive for anti-interferon type I serum antibody. Anti-interleukin-17A levels inversely correlated with the number of manifestations in each patient. This negative correlation may suggest a protective effect of anti-interleukin-17A with a potential therapeutic application.