Practitioner Review: Assessment and treatment of body dysmorphic disorder in young people.

Body dysmorphic disorder (BDD) is a relatively common and highly impairing mental disorder that is strikingly underdiagnosed and undertreated in Child and Adolescent Mental Health Services (CAMHS). The only clinical guidelines for the management of BDD in youth were published nearly 20 years ago, when empirical knowledge was sparse. Fortunately, there has been a surge in research into BDD over the last 10 years, shedding important insights into the phenomenology, epidemiology, assessment and treatment of the disorder in young people. This review aimed to provide an overview of recent research developments of relevance to clinicians and healthcare policymakers. We summarise key findings regarding the epidemiology of BDD in youth, which indicate that the disorder usually develops during teenage years and affects approximately 2% of adolescents at any one point in time. We provide an overview of aetiological research, highlighting that BDD arises from an interplay between genetic and environmental influences. We then focus on screening and assessment strategies, arguing that these are crucial to promote detection and diagnosis of this under-recognised condition. Additionally, we summarise the recommended treatment approaches for BDD in youth, namely cognitive behaviour therapy with or without selective serotonin reuptake inhibitors. The review concludes by highlighting key knowledge gaps and priorities for future research including, but not limited to, better understanding aetiological factors, long-term consequences and treatment.

Internet-Based Treatment of Body Dysmorphic Disorder: Feasibility, Evaluation, and Self-Report Data.

ABSTRACT: Initial findings indicate the effectiveness of internet-based interventions for body dysmorphic disorder (BDD). In order to substantiate these findings, a seven-module guided internet-based intervention was created and examined. We report the mixed data of participants with clinical and subclinical BDD of the treatment group (n = 18). We investigated the feasibility, the quality of the program content, the design and usability, and its effects on symptom severity and related psychopathology. Adherence to the intervention was low and dropout rate high (55.6%). The program content, perceived website usability, and visual aesthetic were rated high. Credibility and expectancy were on a medium level. Satisfaction with appearance improved significantly in the intention-to-treat analysis (d = 0.58). In sum, symptom-related outcomes and program evaluation showed a positive trend albeit the study conduction was difficult. Future programs should investigate the role of additional motivation strategies and more flexible support addressing the known treatment barriers.

A genome-wide association study identifies key modulators of complement factor H binding to malondialdehyde-epitopes.

Genetic variants within complement factor H (CFH), a major alternative complement pathway regulator, are associated with the development of age-related macular degeneration (AMD) and other complementopathies. This is explained with the reduced binding of CFH or its splice variant factor H-like protein 1 (FHL-1) to self-ligands or altered self-ligands (e.g., malondialdehyde [MDA]-modified molecules) involved in homeostasis, thereby causing impaired complement regulation. Considering the critical role of CFH in inhibiting alternative pathway activation on MDA-modified surfaces, we performed an unbiased genome-wide search for genetic variants that modify the ability of plasma CFH to bind MDA in 1,830 individuals and characterized the mechanistic basis and the functional consequences of this. In a cohort of healthy individuals, we identified rs1061170 in CFH and the deletion of CFHR3 and CFHR1 as dominant genetic variants that modify CFH/FHL-1 binding to MDA. We further demonstrated that FHR1 and FHR3 compete with CFH for binding to MDA-epitopes and that FHR1 displays the highest affinity toward MDA-epitopes compared to CFH and FHR3. Moreover, FHR1 bound to MDA-rich areas on necrotic cells and prevented CFH from mediating its cofactor activity on MDA-modified surfaces, resulting in enhanced complement activation. These findings provide a mechanistic explanation as to why the deletion of CFHR3 and CFHR1 is protective in AMD and highlight the importance of genetic variants within the CFH/CFHR3/CFHR1 locus in the recognition of altered-self in tissue homeostasis.

What happens in the course of positive mirror exposure? Effects on eating pathology, body satisfaction, affect, and subjective physiological arousal in patients with anorexia and bulimia nervosa.

OBJECTIVE: Mirror exposure (ME) is a therapeutic technique to improve body image disturbance. However, evidence on the effectiveness of different forms of ME in clinical populations is lacking. The present study therefore analysed effects of ME on trait-like and state measures of body image in patients with anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: The present study therefore analysed effects of ME on trait-like and state measures of body image in patients with anorexia nervosa (AN) and bulimia nervosa (BN). In total, 47 inpatients underwent 3 ME sessions guided by a therapist, with instructions to exclusively verbalise positively about their whole body. Participants completed questionnaires on trait-like eating pathology and body image at the start and end of the study, and instruments on state affect and body satisfaction were administered directly before and after each ME session. Subjective physiological arousal and emotional valence relating to each body part were assessed within each session. RESULTS: The results indicate significant improvements in eating pathology and body image regarding trait-like measures in patients with AN and BN. Concerning state measures, negative affect significantly decreased and body satisfaction increased during ME. Physiological arousal decreased and positively valenced emotions relating to the various body parts increased. CONCLUSIONS: These findings suggest that positively verbalising about one's body during ME improves eating pathology, body image, affect, and subjective physiological arousal, and thus seems to be an effective form of ME.

Appearance-Related Partner Preferences and Body Image in a German Sample of Homosexual and Heterosexual Women and Men.

There is evidence that gender as well as sexual orientation can affect body image. In particular, heterosexual women and homosexual men seem to be more vulnerable to a negative body image compared to homosexual women and heterosexual men. One reason for this may be derived from the fact that heterosexual women and homosexual men try to attract male romantic partners: As men place more importance on physical attractiveness than do women, the pressure to fulfill the sociocultural beauty ideal is thus increased. The present online study investigated differences in appearance-related partner preferences and their associations with measures of body image and eating pathology in homosexual and heterosexual women and men. The non-representative sample consisted of 893 participants (n = 201 lesbian women, n = 192 gay men, n = 349 heterosexual women, and n = 151 heterosexual men), who completed silhouette measures assessing their perception and expectations regarding body fat and muscularity of their own body and the body of a potential romantic partner, as well as questionnaires on drive for thinness, drive for muscularity, and eating pathology. Overall, few differences in appearance-related partner preferences emerged between the four groups. However, compared to heterosexual women, homosexual men appeared to prefer higher muscularity in potential romantic partners, which was also associated with increased drive for thinness and muscularity and increased eating pathology. The present findings indicate that, irrespective of sexual orientation, women and men tend to share similar standards regarding their own and a potential partner's physical appearance, potentially suggesting an increased hegemony of heteronormative beauty ideals in women and men in general.

FHR5 Binds to Laminins, Uses Separate C3b and Surface-Binding Sites, and Activates Complement on Malondialdehyde-Acetaldehyde Surfaces.

Factor H related-protein 5 (CFHR5) is a surface-acting complement activator and variations in the CFHR5 gene are linked to CFHR glomerulonephritis. In this study, we show that FHR5 binds to laminin-521, the major constituent of the glomerular basement membrane, and to mesangial laminin-211. Furthermore, we identify malondialdehyde-acetaldehyde (MAA) epitopes, which are exposed on the surface of human necrotic cells (Homo sapiens), as new FHR5 ligands. Using a set of novel deletion fragments, we show that FHR5 binds to laminin-521, MAA epitopes, heparin, and human necrotic cells (HUVECs) via the middle region [short consensus repeats (SCRs) 5-7]. In contrast, surface-bound FHR5 contacts C3b via the C-terminal region (SCRs8-9). Thus, FHR5 uses separate domains for C3b binding and cell surface interaction. MAA epitopes serve as a complement-activating surface by recruiting FHR5. The complement activator FHR5 and the complement inhibitor factor H both bind to oxidation-specific MAA epitopes and FHR5 competes with factor H for binding. The C3 glomerulopathy-associated FHR21-2-FHR5 hybrid protein is more potent in MAA epitope binding and activation compared with wild-type FHR5. The implications of these results for pathology of CFHR glomerulonephritis are discussed. In conclusion, we identify laminins and oxidation-specific MAA epitopes as novel FHR5 ligands and show that the surface-binding site of FHR5 (SCRs5-7) is separated from the C3b binding site (SCRs8-9). Furthermore, FHR5 competes with factor H for binding to MAA epitopes and activates complement on these modified structures.

Testing the specificity of interpretation biases in women with eating disorder symptoms: An online experimental assessment.

OBJECTIVE: Cognitive biases, such as memory, attention, and interpretation bias, are thought to play a central role in the development and maintenance of eating disorders (EDs). The aim of the present study was to investigate whether the interpretation bias is ED-specific or can be generalized to comorbid disorder-related threats in women with high levels of ED symptoms. METHOD: In an online study, we measured interpretation bias using the modified Sentence Word Association Paradigm (SWAP), comparing women with (n = 39) and without (sub)threshold eating disorders (n = 56). We assessed endorsement and rejection rates as well as reaction times in response to a positive/neutral or a negative ED-specific, social anxiety-specific (SAD), or generalized anxiety-specific (GAD) interpretive word following an ambiguous sentence. RESULTS: In ambiguous situations, women with high ED symptoms selected more negative (p < .001) and fewer positive/neutral ED-related interpretations (p < .001). Negative interpretations were endorsed significantly faster (p < .001), while positive interpretations were rejected faster in this group (p < .001). These women also manifested negative SAD-specific interpretation bias patterns in reaction time measures. Nevertheless, ED severity was best predicted by the endorsement of negative ED-specific stimuli, whereas ED and SAD reaction time measures seemed to have a negligible effect. DISCUSSION: The results indicate that the interpretation bias might be ED-specific. The SWAP can be a useful tool for the further investigation of the etiological relevance of the interpretation bias as well as for the development of modification training interventions.

Are there associations between religious affiliation and drive for muscularity? A cross-sectional survey of young Muslim women, Christian women and atheist women from Germany.

BACKGROUND: Over the last 20 years, society's perception of the ideal female body size in Western cultures has changed from thin to athletic, and many women practice sports to achieve well-toned bodies. However, to date, no study has investigated whether Muslim women who live in a Western country and veil their bodies strive for lean or muscular bodies too. The current cross-sectional survey therefore addressed this question. METHODS: Veiled Muslim women (n = 70), unveiled Muslim women (n = 50), Christian women (n = 79), and atheist women (n = 68) living in Germany answered several questionnaires assessing engagement in sports, body appreciation, and drive for leanness and muscularity. Univariate and multivariate analyses were conducted to compare the four groups. RESULTS: The results of univariate and multivariate analyses showed that Muslim women engaged less in sports and veiled Muslim women reported higher body appreciation than did Christian and atheist women. Although the groups did not differ significantly in drive for muscularity, Muslim women showed lower levels of drive for leanness than did Christian and atheist women. CONCLUSION: Given that Muslim women engaged less in sports and strived less for a lean body compared to Christian and atheist women, a well-toned body might be less important for them. Nevertheless, as being active is beneficial for general health, barriers that prevent Muslim women from engaging in sports should be diminished.

The Body Image Matrix of Thinness and Muscularity-Male Bodies: Development and validation of a new figure rating scale for body image in men.

OBJECTIVE: The study aimed to validate the Body Image Matrix of Thinness and Muscularity-Male Bodies (BIMTM-MB), a two-dimensional figure rating scale consisting of 64 three-dimensional male bodies, arranged in an 8 × 8 grid, with muscularity increasing stepwise on the vertical axis and body fat on the horizontal axis. METHOD: The online sample included 355 men participating in an online survey. Besides the BIMTM-MB, participants completed questionnaires on body-related attitudes, behaviors, and psychopathology. Another 91 men were recruited to examine test-retest reliability of the BIMTM-MB. RESULTS: The BIMTM-MB showed good convergent and criterion validity. Men meeting their own body ideal showed higher body satisfaction and lower body-related psychopathology. Test-retest reliability was high. CONCLUSIONS: The BIMTM-MB proved to be a reliable and valid measure and is recommended for use in research and clinical practice to examine central aspects of male body image.

Pica behaviors in a German community-based online adolescent and adult sample: an examination of substances, triggers, and associated pathology.

PURPOSE: To examine self-reported pica substances, situational triggers for, and associated psychosocial burden of pica eating in adolescents and adults in a Western European population. METHODS: A total of 78 individuals aged 16 years and over, who indicated consuming a substance that in their opinion is not considered as food, participated in an online survey. Two questionnaires assessed eating disorder and general psychopathology, and a third asked about the substances consumed, duration and frequency of consumption, triggers for consumption, emotions thereafter, and interest in treatment. RESULTS: The most frequently reported substances included foods in an uncooked or non-edible form, body parts/fluids, grass, leaves, paper, and earth-like substances, with 54 (69.23%) participants reporting a substance that would qualify as pica substance according to DSM-5. The main triggers for consumption were taste of the substance/indulgence, boredom, curiosity, and release of internal tension. The most common emotion after consumption was relief. Pica eating frequency was not significantly related to eating disorder and general psychopathology (both p > 0.05). A total of 24 individuals considered their pica eating as disruptive, of whom only eight declared an interest in treatment. CONCLUSIONS: The kind of substances consumed is in line with the previous reports in other populations. Pica eating does not seem to be associated with significant psychosocial burden; only a subgroup indicated that they experience it as disruptive and expressed interest in treatment. Nevertheless, for these individuals, triggers for pica eating and emotions thereafter might provide first hints for the development of interventions. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

How do you feel when you check your body? Emotional states during a body-checking episode in normal-weight females.

PURPOSE: Cognitive-behavioral theories posit that body checking decreases negative emotions, but increases levels of arousal. However, few studies have investigated the effects of body checking on the course of emotional states. Therefore, the current study examined how normal-weight females with higher and lower eating, weight, and shape concerns feel during a checking episode of their most-liked and least-liked body parts. METHODS: In an online design, levels of negative emotions and arousal were retrospectively assessed before, during, immediately after, and 15 min after an individually remembered body-checking episode. Participants (N = 355) also rated their subjective satisfaction with specific body parts. RESULTS: Levels of negative emotions were lower 15 min after the checking episode of most-liked and least-liked body parts than before the episode. However, negative emotions increased during the checking episode of least-liked body parts, but subsided thereafter. The levels of arousal increased during the checking episodes of most-liked and least-liked body parts and decreased afterwards, and females with higher concerns reported greater levels of arousal than females with lower concerns. Furthermore, females with higher concerns reported more body checking than those with lower concerns. CONCLUSIONS: The results support the assumptions of the cognitive-behavioral theories, as body checking led to a decrease in negative emotions in the longer term, and levels of arousal increased during the checking episode. The greater levels of arousal in females with higher concerns, and their pronounced body-checking behavior, might enhance their existing concerns and increase the risk of disordered eating. LEVEL OF EVIDENCE: Level V, descriptive study.

Efficacy of psychotherapies and pharmacotherapies for Bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN), a mental disorder that causes significant impairment, can be treated with psychological, pharmacological, nutrition-based and self-help interventions. We conducted a pre-registered meta-analysis of randomized-controlled trials (RCTs) to assess the efficacy of these interventions in up to 19 different interventions. METHODS: Database search terms were combined for BN and RCTs from database inception to March 2017. Abstinence from binge eating episodes, compensatory behaviors, the absence of a BN diagnosis and reduction of symptom severity were considered as primary outcome variables, reduction of self-reported eating pathology and depression served as secondary outcome variables. Retrieved RCTs were meta-analyzed using fixed and random effects models. RESULTS: RCT (79 trials; 5775 participants) effects post-treatment revealed moderate to large intervention effects for psychotherapy [mostly cognitive-behavioral therapy (CBT)] for primary outcome variables. Slightly reduced effects were obtained for self-help and moderate effects for pharmacotherapy. Similarly, psychotherapy yielded large to very large effects in regard to secondary outcome variables, while moderate to large effects were observed for self-help, Pharmacotherapy and combined therapies. Meta-analyses for the pre to post changes within group confirmed these findings. Additionally, follow-up analyses revealed the sustainability of psychotherapies in terms of large effects in primary outcome criteria, while these effects were moderate for self-help, pharmacotherapy, and combined therapies. CONCLUSIONS: Most psychological and pharmacological interventions revealed to be effective in BN treatment. Taking effect size, sustainability of the intervention, as well as the consistency of findings and available evidence into consideration, CBT can be recommended as the best intervention for the initial treatment of BN.

Implicit attitudes toward dieting and thinness distinguish fat-phobic and non-fat-phobic anorexia nervosa from avoidant/restrictive food intake disorder in adolescents.

OBJECTIVE: The majority of individuals with anorexia nervosa (AN) have a fat-phobic (FP-AN) presentation in which they explicitly endorse fear of weight gain, but a minority present as non-fat-phobic (NFP-AN). Diagnostic criteria for avoidant/restrictive food intake disorder (ARFID) specifically exclude fear of weight gain. Differential diagnosis between NFP-AN and ARFID can be challenging and explicit endorsements do not necessarily match internal beliefs. METHOD: Ninety-four adolescent females (39 FP-AN, 13 NFP-AN, 10 low-weight ARFID, 32 healthy controls [HC]) completed implicit association tests (IATs) categorizing statements as pro-dieting or non-dieting and true or false (questionnaire-based IAT), and images of female models as underweight or normal-weight and words as positive or negative (picture-based IAT). We used the Eating Disorder Examination to categorize FP- versus NFP-AN presentations. RESULTS: Individuals with FP-AN and NFP-AN demonstrated a stronger association between pro-dieting and true statements, whereas those with ARFID and HCs demonstrated a stronger association between pro-dieting and false statements. Furthermore, while all groups demonstrated a negative implicit association with underweight models, HC participants had a significantly stronger negative association than individuals with FP-AN and NFP-AN. DISCUSSION: Individuals with NFP-AN exhibited a mixed pattern in which some of their implicit associations were consistent with their explicit endorsements, whereas others were not, possibly reflecting a minimizing response style on explicit measures. In contrast, individuals with ARFID demonstrated implicit associations consistent with explicit endorsements. Replication studies are needed to confirm whether the questionnaire-based IAT is a promising method of differentiating between restrictive eating disorders that share similar clinical characteristics.

Double standards in body evaluation? The influence of identification with body stimuli on ratings of attractiveness, body fat, and muscle mass.

Although it is well documented that women evaluate their own body differently from other bodies, it remains unclear whether this discrepancy is based on double standards because of identity or on objective differences between these bodies. The aim of this study was therefore to test whether women apply double standards depending on a body's identity when evaluating the same bodies presented with different faces. Average-weight women (N = 104) rated body attractiveness, body fat, and muscle mass of thin, average-weight, overweight, athletic, and hypermuscular bodies with either another female's face or their own face. With their own face, subjects rated overweight bodies as more unattractive, higher in body fat and lower in muscle mass than with another female's face. However, for non-overweight bodies, body ratings did not differ depending on body identity. Based on the self-deprecating double standards for overweight bodies, a body-related identity bias might be considered in theoretical models of body image.Level of evidence Level V, descriptive study.

Double standards in body evaluation? How identifying with a body stimulus influences ratings in women with anorexia nervosa and bulimia nervosa.

OBJECTIVE: Women with eating disorders (ED) evaluate their own body more negatively than do women without ED. However, it is unclear whether this negative rating is due to objective bodily features or different standards for one's own body and others' bodies. Therefore, the purpose of this study was to examine whether women with ED apply double standards when rating bodies by disentangling the objective features of one's own body from the feelings of ownership. METHOD: We presented n = 34 women with anorexia nervosa, n = 31 women with bulimia nervosa, and n = 114 healthy controls with pictures of thin, average-weight, overweight, athletic, and hypermuscular bodies. Identity was manipulated by showing each body once with the participant's own face and once with the face of another woman. Participants were instructed to report their emotional state according to valence and arousal and to rate body attractiveness, body fat, and muscle mass. RESULTS: Women with anorexia nervosa and bulimia nervosa displayed greater self-deprecating double standards in body fat rating than did women without ED, as quantified by the difference between the ratings of the same body with one's own versus another woman's face. Double standards reflected in valence, arousal and attractiveness ratings were significantly more pronounced in women with anorexia nervosa than in women without ED. DISCUSSION: The double standards found may be due to an activation of dysfunctional self-related body schemata, which distort body evaluation depending on identity. Double standards related to body fat were characteristic for women with ED, but not for women without ED.

Correction to: Prevalence of pica and rumination behaviors in German children aged 7-14 and their associations with feeding, eating, and general psychopathology: a population-based study.

n the original publication, under the discussion section.

Prevalence of pica and rumination behaviors in German children aged 7-14 and their associations with feeding, eating, and general psychopathology: a population-based study.

Despite potentially severe medical consequences of pica and rumination disorder (RD), little is known about their prevalence and association with other psychopathology in childhood. As a part of a larger population-based study, 804 children aged 7-14 years and their parents were asked about their experience of pica and RD behaviors, and associated eating, feeding and general psychopathology. A total of 12.31 and 11.49% of the participants reported having engaged in pica or RD behaviors, respectively, at least once. Recurring pica or RD behaviors had been experienced by 4.98 and 1.49% of the participants, respectively. The behaviors showed a significant but small correlation with one another (r = 0.28, p < 0.01). Correlations with symptoms of avoidant/restrictive food intake disorder (ARFID) were significant but small (pica: r = 0.18, RD: r = 0.27, both p < 0.01). Prevalence rates of recurring pica behavior were significantly increased if recurring RD was present (58.33%), and also vice versa (17.50%). The prevalence rates of recurrent pica and RD behaviors were also increased in the presence of an ARFID diagnosis (both behaviors 12.0%). However, correlations with restraint and eating, weight, and shape concern were non-significant (all p > 0.05). Additionally, RD behavior was positively correlated with emotional and conduct problems (r = 0.15 and 0.22, both p < 0.01), and both behaviors were negatively correlated with prosocial behavior (r = -  0.10 and - 0.09, both p < 0.05). Our findings underscore the clinical significance of pica and RD behaviors. More research is warranted on both disorders and their association and relation with ARFID to deepen the understanding of their presentation and to ascertain diagnostic validity.

Body Covering and Body Image: A Comparison of Veiled and Unveiled Muslim Women, Christian Women, and Atheist Women Regarding Body Checking, Body Dissatisfaction, and Eating Disorder Symptoms.

Although Islam is the fastest growing religion worldwide, only few studies have investigated body image in Muslim women, and no study has investigated body checking. Therefore, the present study examined whether body image, body checking, and disordered eating differ between veiled and unveiled Muslim women, Christian women, and atheist women. While the groups did not differ regarding body dissatisfaction, unveiled Muslim women reported more checking than veiled Muslim and Christian women, and higher bulimia scores than Christian. Thus, prevention against eating disorders should integrate all women, irrespective of religious affiliation or veiling, with a particular focus on unveiled Muslim women.

Are eating disorders "all about control?" The elusive psychopathology of nonfat phobic presentations.

OBJECTIVE: There are a subset of individuals with eating disorders (EDs) who do not overevaluate body shape/weight (i.e., nonfat phobic ED; NFP-ED). According to the transdiagnostic cognitive-behavioral conceptualization of EDs, a need for control, in general, is hypothesized as the core psychopathology of NFP-EDs, with shape- and weight-related motivations for ED behavior merely superimposed in FP-ED presentations. This study tested the need for control as motivation for restriction in NFP-ED, using items aimed at assessing control from the Eating Disorder Examination (EDE) Restraint scale. METHOD: Females ages 13-27 years consecutively admitted to residential treatment completed the EDE, Eating Disorder Inventory-3 Drive for Thinness subscale (EDI-DFT), and other self-report measures of psychopathology. We included patients with DSM-5 EDs, but excluded patients with avoidant/restrictive food intake disorder. Twenty participants had NFP-ED (≤14 on EDI-DFT) and 124 had fatphobic ED (FP-ED; >14 on EDI-DFT). RESULTS: NFP-ED scored significantly lower than FP-ED on EDE Restraint scale shape/weight [χ2 (1) = 10.73-35.62, p's < .01] and on control items [χ2 (1) = 10.72-20.62, p's < .01], in addition to scoring lower on measures of general psychopathology and impairment. DISCUSSION: Findings suggest those with NFP-ED report lower psychopathology overall and the new EDE Restraint scale control items do not capture additional motivation for restriction beyond that captured in the original Restraint scale shape/weight items. Future research should examine whether this latter finding is due to a minimizing response style in NFP-ED, an incomplete capture of desire for control by the EDE assessment method, or indeed reflects that need for control does not motivate restriction in NFP-EDs.

Complement Factor H-Related 5-Hybrid Proteins Anchor Properdin and Activate Complement at Self-Surfaces.

C3 glomerulopathy (C3G) is a severe kidney disease for which no specific therapy exists. The causes of C3G are heterogeneous, and defective complement regulation is often linked to C3G pathogenesis. Copy number variations in the complement factor H-related (CFHR) gene cluster on chromosome 1q32 and CFHR5 mutant proteins associate with this disease. Here, we identified CFHR5 as a pattern recognition protein that binds to damaged human endothelial cell surfaces and to properdin, the human complement activator. We found the two N-terminal short consensus repeat domains of CFHR5 contact properdin and mediate dimer formation. These properdin-binding segments are duplicated in two mutant CFHR5 proteins, CFHR2-CFHR5Hyb from German patients with C3G and CFHR5Dup from Cypriot patients with C3G. Each of these mutated proteins assembled into large multimeric complexes and, compared to CFHR5, bound damaged human cell surfaces and properdin with greater intensity and exacerbated local complement activation. This enhanced surface binding and properdin recruitment was further evidenced in the mesangia of a transplanted and explanted kidney from a German patient with a CFHR2-CFHR5Hyb protein. Enhanced properdin staining correlated with local complement activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro This gain of function in complement activation for two disease-associated CFHR5 mutants describes a new disease mechanism of C3G, which is relevant for defining appropriate treatment options for this disorder.