Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits.

T follicular helper (TFH) cells are a distinct type of CD4+ T cells that are essential for most antibody and B lymphocyte responses. TFH cell regulation and dysregulation is involved in a range of diseases. Bcl-6 is the lineage-defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl-6 controls TFH biology has largely remained unclear, at least in part due to the intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl-6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function, including migration, costimulation, inhibitory receptors and cytokines, via multiple repressor-of-repressor gene circuits.

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens.

How precursor frequencies and antigen affinities impact interclonal B cell competition is a particularly relevant issue for candidate germline-targeting HIV vaccine designs because of the in vivo rarity of naive B cells that recognize broadly neutralizing epitopes. Knowing the frequencies and affinities of HIV-specific VRC01-class naive human B cells, we transferred B cells with germline VRC01 B cell receptors into congenic recipients to elucidate the roles of precursor frequency, antigen affinity, and avidity on B cell responses following immunization. All three factors were interdependently limiting for competitive success of VRC01-class B cells. In physiological high-affinity conditions using a multivalent immunogen, rare VRC01-class B cells successfully competed in germinal centers (GC), underwent extensive somatic hypermutation, and differentiated into memory B cells. The data reveal dominant influences of precursor frequency, affinity, and avidity for interclonal GC competition and indicate that germline-targeting immunogens can overcome these challenges with high-affinity multimeric designs.

Sexual growth and destiny beliefs: Longitudinal associations with dyadic coping among couples seeking medically assisted reproduction.

BACKGROUND: Medically assisted reproduction is a vulnerable time for couples' sexual health. Believing that sexual challenges can be worked through (i.e., sexual growth beliefs) or that these challenges indicate incompatibility (i.e., sexual destiny beliefs) may be related to dyadic coping-the strategies couples use to cope-with the physical and psychological stressors of medically assisted reproduction. AIM: In the current study we aimed to examine the longitudinal associations between typical (i.e., average) levels of sexual growth and destiny beliefs and positive and negative facets of dyadic coping and how greater than typical levels of these constructs predicted each other across time. METHODS: Couples (n = 219) seeking medically assisted reproduction were recruited for an online longitudinal, dyadic study. OUTCOMES: Couples completed online measures of sexual growth and destiny beliefs and positive and negative dyadic coping at baseline, 6-and 12-months. RESULTS: Random intercept cross-lagged panel models demonstrated that at the within-person level, reporting higher sexual growth beliefs at baseline, relative to their average across time points, was associated with lower negative dyadic coping at 6 months. Higher negative dyadic coping at 6 months, relative to their average, was linked to lower sexual growth beliefs at 12-months. When individuals reported higher sexual destiny beliefs at 6-months, relative to their average, they and their partners reported higher negative dyadic coping at 12 -months. At the between-person level, higher overall levels of sexual destiny beliefs were related to higher overall levels of negative dyadic coping. No associations with positive dyadic coping were identified. CLINICAL IMPLICATIONS: Couples may benefit from identifying and reducing unhelpful beliefs about sex and negative dyadic coping. STRENGTHS AND LIMITATIONS: Strengths of this study include our large, inclusive sample, engagement of community partners, and novel analytical approach to assess change over time. However, following couples in 6-month increments and not using questionnaires specific to medically assisted reproduction may have limited our ability to detect nuanced changes that couples experience during this time. CONCLUSION: Lower sexual growth and higher sexual destiny beliefs may promote couples' engagement in less adaptive coping behaviors as they seek medically assisted reproduction.

Comparing Self-Reported Pain During Intercourse and Pain During a Standardized Gynecological Exam at 12- and 24-Month Postpartum.

BACKGROUND: There is limited information about the physical indicators and biopsychosocial predictors of self-reported pain during intercourse and pain during a gynecological examination at 12- and 24-month following childbirth. AIM: This longitudinal study aimed to (i) Compare the findings from gynecological exams at 12- and 24-month postpartum for women with minimal vs clinically significant pain during intercourse; (ii) Assess the biomedical and psychosocial correlates of self-reported pain during intercourse and the vestibular pain index (VPI) from the cotton-swab test at 12- and 24-month postpartum; (iii) Establish the relationship between self-reported pain during intercourse and the cotton-swab test. METHODS: Women (N = 97 at 12 months postpartum and N = 44 at 24-month postpartum) recruited from a local women's hospital completed online surveys in their first trimester of pregnancy and at 12- and 24-month postpartum to assess pain during intercourse and biopsychosocial variables. Those with clinically significant (pain ≥4/10 on a visual analogue scale) were matched with those reporting minimal pain (pain <3/10) and underwent a gynecological exam including a cotton-swab test. Descriptive analyses, multiple regressions, and bivariate correlations were conducted to address each of the study aims, respectively. MAIN OUTCOME MEASURES: (i) Findings from the gynecological examination (ii) Numerical rating scale for the VPI; (iii) Visual analogue scale of pain during intercourse. RESULTS: The majority of women in both pain groups had normal physical findings in the gynecological exam. Greater sexual distress and pain catastrophizing at 12- and 24-month postpartum were significantly associated with greater pain during intercourse at each time-point, respectively. Greater pain catastrophizing at 12 months postpartum was significantly associated with greater pain during the cotton-swab test at that time-point. Lower relationship satisfaction at 12 months postpartum was associated with greater VPI ratings at 24 months postpartum. Pain during intercourse and the VPI were moderately and positively correlated. CLINICAL IMPLICATIONS: Addressing psychosocial variables may interrupt the maintenance of postpartum pain. Following an initial assessment, self-reported pain intensity may be a suitable proxy for repeated examinations. STRENGTHS & LIMITATIONS: This study is the first to describe the physical findings and psychosocial predictors of pain during intercourse and the VPI at 12- and 24-month postpartum. The homogenous and small sample may limit generalizability. CONCLUSION: There were no observable physical indicators of clinically significant postpartum pain during intercourse. Psychosocial variables were linked to women's greater postpartum pain during intercourse and VPI ratings. Rossi MA, Vermeir E, Brooks M, et al. Comparing Self-Reported Pain During Intercourse and Pain During a Standardized Gynecological Exam at 12- and 24-Month Postpartum. J Sex Med 2022;19:116-131.

A Longitudinal Investigation of Couples' Sexual Growth and Destiny Beliefs in the Transition to Parenthood.

Beliefs about sexuality tend to become more salient during sexual challenges and are associated with how individuals respond to these difficulties and, in turn, their sexual well-being. The transition to parenthood is marked by significant changes to couples' sexuality. As such, this period of vulnerability may be an important context in which these beliefs impact how couples manage sexual stressors and may have implications for their sexual well-being. In a longitudinal dyadic study, we examined whether couples' sexual growth beliefs (e.g., beliefs that sexual problems can be resolved through effort) and sexual destiny beliefs (e.g., beliefs that sexual problems reflect incompatibility with their partner) correspond with changes to various facets of couples' sexual well-being over time. First-time parent couples (N = 203) completed online surveys assessing these beliefs in pregnancy (32 weeks) and measures of sexual well-being (satisfaction, desire, and distress) in pregnancy (20 and 32 weeks) and across the postpartum period (3, 6, 9, 12 months). Dyadic latent growth curve models showed that expectant mothers who reported stronger sexual destiny beliefs in pregnancy reported higher sexual distress and lower sexual satisfaction at 3 months postpartum. When partners reported stronger sexual destiny beliefs in pregnancy, both they and new mothers reported greater sexual desire at 3 months postpartum. Unexpectedly, partners' higher sexual growth beliefs in pregnancy predicted mothers' lower sexual desire at 3 months postpartum. Sexual growth and destiny beliefs were not associated with change in couples' sexual well-being beyond 3 months postpartum. Findings shed light on the potential benefits and costs of sexual growth and destiny beliefs for couples' sexual well-being early in the postpartum period, but not over time.

Sexual Function and Satisfaction in Couples with Infertility: A Closer Look at the Role of Personal and Relational Characteristics.

BACKGROUND: Research to date suggests that couples undergoing assisted reproductive technology (ART) are at a high risk of experiencing sexual difficulties. AIM: This dyadic cross-sectional study aimed to provide a better understanding of the infertility-specific personal (ie, emotional, mind-body) and relational stressors associated with the sexual desire, orgasm, arousal, and sexual satisfaction of infertile couples seeking ART. METHODS: The sample included 185 mixed-sex infertile couples seeking ART. Participants completed online the Fertility Quality of Life tool and either the Female Sexual Function Index or the International Index of Erectile Function. Data were analyzed using path analyses based on the Actor-Partner Interdependence Model. OUTCOMES: Individuals' own and their partners' sexual function (desire, orgasm, arousal domains) and sexual satisfaction. RESULTS: For men and women, infertility-related emotional stressors were associated with their own and their partner's lower sexual desire. For women, experiencing greater infertility-related emotional stressors was also associated with their partner's lower sexual satisfaction. While experiencing greater infertility-related mind-body stressors was not associated with men and women's own sexual desire, arousal, orgasm, and satisfaction, for women, it was associated with their partner's lower sexual arousal. Lastly, for men and women, infertility-related relational stressors were associated with their own lower sexual arousal, as well as with their own and their partner's lower sexual satisfaction. For women, experiencing greater relational stressors was also associated with their own lower sexual desire and orgasm. CLINICAL IMPLICATIONS: Interventions addressing the emotional, mind-body, and relational spheres of infertile couples seeking ART may help facilitate improvements in sexual function and satisfaction and better serve their needs. STRENGTHS & LIMITATIONS: This study included a large sample of couples. Our sample was heterogeneous with regards to couples' cause of infertility and treatment stage. The use of an infertility-related measure allowed us to better capture personal and relational stressors specific to couples seeking ART. Given the cross-sectional design of our study, causality between infertility-related stressors and sexual function and satisfaction cannot be inferred. Our sample included predominantly White, mixed-sex individuals with a high level of education, which may reduce the generalizability of our findings. CONCLUSION: Couples' subjective experience of infertility and treatment (personal and relational stressors) seems to be strongly associated with their sexual health, allowing us to identify potential targets of intervention with couples seeking ART. S.E. Amiri, A Brassard, N.O. Rosen, et al. Sexual Function and Satisfaction in Couples with Infertility: A Closer Look at the Role of Personal and Relational Characteristics. J Sex Med 2021;18:1984-1997.

A Descriptive and Longitudinal Analysis of Pain During Intercourse in Pregnancy.

INTRODUCTION: Pain during vaginal intercourse in pregnancy has largely been ignored despite physiological and psychological components of pregnancy that may be associated with its onset and persistence. AIM: The current study aimed to determine the prevalence and the characteristics of clinically significant pain during intercourse in the second (18-24 weeks) and third (32-36 weeks) trimesters of pregnancy. METHODS: Pregnant women (N = 501) recruited from a local women's hospital completed an online survey in the second and third trimesters of their pregnancy regarding the presence, intensity, and characteristics of pain during intercourse. Women with clinically significant pain (ie, pain greater than or equal to 4 of 10 on a numerical rating scale) were grouped according to whether the pain was resolved, persistent, or new onset across the 2 pregnancy time points. Following guidelines outlined by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), we conducted a descriptive analysis assessing the intensity and characteristics (eg, quality, onset, degree of improvement over time, and treatment strategies utilized) of clinically significant pain during intercourse. MAIN OUTCOME MEASURE: The main outcome measures in this study were the prevalence, intensity, and characteristics of clinically significant pain during intercourse. RESULTS: Overall, 21% of pregnant women (106/501) reported clinically significant pain during intercourse. We found that 22% (N = 16/106) of women who had this pain at 20 weeks reported that it had resolved at 34 weeks, 33% (40/106) reported persistent pain at both time points, and 46% (50/106) reported new onset of pain during intercourse at 34 weeks. The majority of women across all pain groups reported that the pain began during pregnancy and remained at the same intensity. Most women reported not using any pain management strategies to cope with their pain. CLINICAL IMPLICATIONS: One in 5 women experienced clinically significant pain during intercourse in pregnancy, with the majority of women not seeking treatment. STRENGTHS & LIMITATIONS: This study is the first to comprehensively assess and describe the prevalence and characteristics of clinically significant pain during intercourse across 2 time points in pregnancy using IMMPACT guidelines. Small sample sizes in our pain groups may limit the generalizability of pain characteristics. CONCLUSION: Findings suggest that many pregnant women in this study experienced significant pain during intercourse in pregnancy. Understanding the characteristics of this pain may improve its identification by health care providers and inform better prevention and treatment recommendations. Rossi MA, Mooney KM, Binik YM, et al. A Descriptive and Longitudinal Analysis of Pain During Intercourse in Pregnancy. J Sex Med 2019;16:1966-1977.

Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease.

OBJECTIVES: There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. METHODS: We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). RESULTS: Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. CONCLUSIONS: This study indicates that <5% patients with sCJD develop serum antibodies to these neuronal antigens and, when positive, only at low titres. By contrast, three patients referred with possible prion disease had a clinical picture in keeping with autoimmune encephalitis and very high VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution.

Perceived financial burden is indirectly linked to sexual well-being via quality of life among couples seeking medically assisted reproduction.

Introduction: Medically assisted reproduction is a difficult treatment process for couples both financially and sexually. Yet, these two domains have not been examined together among couples seeking treatment, leaving couples and practitioners without guidance on how to address these domains together. Methods: In line with Couples and Finance Theory, we tested the hypothesis that perceived financial burden and couple income would predict quality of life during medically assisted reproduction, which would then predict four domains of sexual well-being (i.e., sexual satisfaction, desire, distress, and frequency). We also examined if the results differed by treatment status-that is, between partners who were receiving treatment and those who were not. Cross-sectional data from 120 couples who had undergone medically assisted reproduction in the past six months were analyzed via structural equation modeling through an actor-partner interdependence mediation model. Results: An individual's greater perceived financial burden predicted their own lower quality of life during medically assisted reproduction, which in turn predicted their lower sexual satisfaction, desire and distress, as well as their partner's lower sexual satisfaction. Household income did not indirectly predict any sexual well-being domains, and results regarding treatment status were inconclusive. Discussion: Clinicians can discuss with couples how perceived financial strain of medically assisted reproduction affects their quality of life and what ramifications that may have for their sexual well-being.

An Internet-Based Cognitive Behavioral Therapy Program for Anxiety and Depression (Tranquility): Adaptation Co-design and Fidelity Evaluation Study.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) is a necessary step toward increasing the accessibility of mental health services. Yet, few iCBT programs have been evaluated for their fidelity to the therapeutic principles of cognitive behavioral therapy (CBT) or usability standards. In addition, many existing iCBT programs do not include treatments targeting both anxiety and depression, which are commonly co-occurring conditions. OBJECTIVE: This study aims to evaluate the usability of Tranquility-a novel iCBT program for anxiety-and its fidelity to CBT principles. This study also aims to engage in a co-design process to adapt Tranquility to include treatment elements for depression. METHODS: CBT experts (n=6) and mental health-informed peers (n=6) reviewed the iCBT program Tranquility. CBT experts assessed Tranquility's fidelity to CBT principles and were asked to identify necessary interventions for depression by using 2 simulated client case examples. Mental health-informed peers engaged in 2 co-design focus groups to discuss adaptations to the existing anxiety program and the integration of interventions for depression. Both groups completed web-based surveys assessing the usability of Tranquility and the likelihood that they would recommend the program. RESULTS: The CBT experts' mean rating of Tranquility's fidelity to CBT principles was 91%, indicating a high fidelity to CBT. Further, 5 out of 6 CBT experts and all mental health-informed peers (all participants: 11/12, 88%) rated Tranquility as satisfactory, indicating that they may recommend Tranquility to others, and they rated its usability highly (mean 76.56, SD 14.07). Mental health-informed peers provided suggestions on how to leverage engagement with Tranquility (eg, adding incentives and notification control). CONCLUSIONS: This preliminary study demonstrated the strong fidelity of Tranquility to CBT and usability standards. The results highlight the importance of involving stakeholders in the co-design process and future opportunities to increase engagement.

A Systematic Review of the Prospective Relationship between Child Maltreatment and Chronic Pain.

OBJECTIVE: The present systematic review aimed to evaluate the association between childhood maltreatment and chronic pain, with specific attention to the temporal nature of the relationship and putative moderators, including, the nature (type), timing of occurrence, and magnitude of maltreatment; whether physical harm or injury occurred; and whether post-traumatic stress disorder (PTSD) subsequently developed. METHOD: We included studies that measured the prospective relationship between child maltreatment and pain. Medline, EMBASE, PsycINFO, and CINAHL were searched electronically up to 28 July 2019. We used accepted methodological procedures common to prognosis studies and preregistered our review (PROSPERO record ID 142169) as per Cochrane review recommendations. RESULTS: Nine studies (17,340 participants) were included in the present review. Baseline participant age ranged from 2 years to more than 65 years. Follow-up intervals ranged from one year to 16 years. Of the nine studies included, three were deemed to have a high risk of bias. With the exception of one meta-analysis of three studies, results were combined using narrative synthesis. Results showed low to very low quality and conflicting evidence across the various types of maltreatment, with the higher quality studies pointing to the absence of direct (non-moderated and non-mediated) associations between maltreatment and pain. PTSD was revealed to be a potential mediator and/or moderator. Evidence was not found for other proposed moderators. CONCLUSIONS: Overall, there is an absence of evidence from high quality studies of an association between maltreatment and pain. Our results are limited by the small number of studies reporting the relationship between child maltreatment and pain using a prospective design. High quality studies, including prospective cohort studies and those that assess and report on the moderators described above, are needed to advance the literature.

Biased Partner Perceptions of Women's Pain Self-Efficacy in Postpartum Pain During Intercourse: A Dyadic Longitudinal Examination.

Postpartum pain during intercourse is a prevalent and distressing problem that has substantial consequences for affected couples. Partner perceptions-such as how partners perceive women's pain self-efficacy-contribute to an individual's pain experience. This study examined whether partners under- or over-estimate women's intercourse pain self-efficacy at 3-months postpartum and the implications of this bias for women's pain and couples' sexual functioning at 3- and 6-months postpartum. Women who reported pain during intercourse and their partners (N = 89 couples) completed online measures assessing pain self-efficacy (own or partner perceptions), pain intensity, and sexual functioning at 3- and 6-months postpartum. Analyses were based on the Truth and Bias Model of Judgement and Response Surface Analysis. Partners were accurate in their estimates of women's pain self-efficacy (ie, their estimates were positively correlated with women's), but they also underestimated it by perceiving women to be less efficacious than women themselves reported. When couples showed greater agreement for lower levels of pain self-efficacy at 3 months, women reported greater pain intensity and both partners reported poorer sexual functioning at 3- and 6-months postpartum. Findings may inform interventions that promote pain self-efficacy to improve partner support and couples' sexual functioning. PERSPECTIVE: When women report-and their partners perceive-low levels of women's self-efficacy for managing painful intercourse, women report greater postpartum pain during intercourse and couples indicate poorer sexual functioning. These findings suggest that interventions aimed at promoting couples' agreement at high pain self-efficacy may improve their adjustment to postpartum pain.

Neuronal Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes.

The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Aß, and for understanding how neuronal activity can modulate diurnal processes.

Powerhouse of the mind: mitochondrial plasticity at the synapse.

Neurons are highly polarized cells with extraordinary energy demands, which are mainly fulfilled by mitochondria. In response to altered neuronal energy state, mitochondria adapt to enable energy homeostasis and nervous system function. This adaptation, also called mitochondrial plasticity, can be observed as alterations in the form, function and position. The primary site of energy consumption in neurons is localized at the synapse, where mitochondria are critical for both pre- and postsynaptic functions. In this review, we will discuss molecular mechanisms regulating mitochondrial plasticity at the synapse and how they contribute to information processing within neurons.

Vulvodynia: a consideration of clinical and methodological research challenges and recommended solutions.

Vulvodynia, an idiopathic chronic vulvar pain, is a prevalent genital pain condition that results in significant impairment to sexual, relational, and psychological functioning of affected women and their romantic partners. Despite its high prevalence, there remain gaps in knowledge and health care access for women coping with vulvodynia, given its varied clinical presentation and no widely accepted treatment protocol. The past several decades have seen important advancements in understanding vulvodynia and developing effective treatments; however, progress has been impeded due to clinical and methodological challenges in conducting research with this vulnerable population. This review presents a brief overview of vulvodynia correlates, consequences, etiology, and treatment, and then turns its attention to considering the clinical and methodological challenges that hinder vulvodynia research. Identifying these barriers alongside potential mitigating solutions is essential to developing empirically supported treatments for all women affected by vulvodynia, across all age and minority groups. Potential solutions will require researchers to broaden eligibility criteria, examine subgroups of women, and expand definitions of treatment outcomes, and may be best facilitated by more active collaboration among research groups and across relevant disciplines. Engagement in these solutions may contribute to more representative findings and the development and dissemination of empirically based treatment options for this complex pain condition.

Clinical relevance of voltage-gated potassium channel­complex antibodies in children.

OBJECTIVE: To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). METHODS: Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients' condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab­positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. RESULTS: VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. CONCLUSION: Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.