Article
Immunology
Margrethe Flesvig Holt, Annika E. Michelsen, Negar Shahini, Elisabeth Bjorkelund, Christina Holt Bendz, Richard J. Massey, Camilla Schjalm, Bente Halvorsen, Kaspar Broch, Thor Ueland, Lars Gullestad, Per H. Nilsson, Pal Aukrust, Tom Eirik Mollnes, Mieke C. Louwe
Summary: In patients with heart failure, the alternative pathway of the complement system is activated, but not the terminal pathway. Plasma levels of factor B and C3 convertase C3bBbP are elevated in these patients, but not associated with mortality during follow-up.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah Murray, Beiying Qiu, Sze Yuan Ho, Xiaomeng Wang
Summary: CFB is a crucial catalytic element in the alternative pathway of complement, playing a key role in ocular angiogenesis by promoting blood vessel formation through mediating the VEGF signaling pathway. This study provides compelling evidence for the involvement of CFB in driving ocular neovascularization in a VEGF-dependent manner, suggesting potential therapeutic targets for blinding eye diseases characterized by pathological angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Genetics & Heredity
Feng-mei Wang, Yan Yang, Xiao-liang Zhang, Yan-li Wang, Yan Tu, Bi-Cheng Liu, Bin Wang
Summary: CFB variants have been found to play a causative role in C3 glomerulopathy and aHUS, while the simultaneous presence of CFB and COL4A5 variants is rare. The cases presented here highlight the significant impact of genetic analyses in diagnosing and understanding familial renal diseases, with siblings showing varying clinical manifestations based on their inherited variants.
FRONTIERS IN GENETICS
(2021)
Review
Immunology
Anna Schubart, Stefanie Flohr, Tobias Junt, Joerg Eder
Summary: Dysregulation of the alternative complement pathway can lead to various diseases, and inhibitors targeting central proteases of the pathway are being developed as therapeutics. These inhibitors have the potential to treat complement-mediated diseases in both systemic and peripheral tissues, and may also be effective in inhibiting complement activation in the central nervous system.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Clinical Neurology
Elle Levit, Janice Leon, Matthew R. Lincoln
Summary: A 36-year-old man with recurring fever, headache, mental status changes, and focal neurologic deficits was found to have extensive white matter lesions on MRI. Complement factor abnormalities, including persistently low C3 and factor B, and absence of alternative complement pathway activity were detected. Biopsy results showed neutrophilic vasculitis. Genetic testing revealed a pathogenic homozygous variant in complement factor I (CFI). Treatment with IL-1β inhibition has resulted in the patient's stability. Complement factor I deficiency is a rare disorder that should be considered in patients with atypical relapsing neurologic disease associated with neutrophilic pleocytosis.
Article
Biochemistry & Molecular Biology
Alexandra E. Butler, Abu Saleh Md Moin, Thozhukat Sathyapalan, Stephen L. Atkin
Summary: In this study, the complement system in polycystic ovary syndrome (PCOS) was comprehensively evaluated. The results showed an upregulation of complement system components, which was offset by the concurrent upregulation of its inhibitors. These changes were partially explained by BMI, hyperandrogenemia, and insulin resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medical Laboratory Technology
Maria Alice V. Willrich, Karin M. P. Braun, Ann M. Moyer, David H. Jeffrey, Ashley Frazer-Abel
Summary: The complement system is crucial for human defense against microbial pathogens, maintaining internal balance and fighting infection/inflammation. Laboratory testing is important for diagnosing suspected complement deficiencies and diseases related to complement dysregulation, focusing on complement lytic activity and component concentrations.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Sheila Cabezas-Falcon, Aidan J. Norbury, Jarrod Hulme-Jones, Sonja Klebe, Penelope Adamson, Penny A. Rudd, Suresh Mahalingam, Li-Ching Ong, Sylvie Alonso, David L. Gordon, Jillian M. Carr
Summary: The study revealed that in a mouse model of dengue, changes in factor B and factor H were observed following DENV infection, with terminal disease associated with complement activation. The AG129 mouse model demonstrates similar changes in FB and FH as in humans, but lacks key human-specific and IFN-dependent responses.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Cell Biology
Alexandra E. Butler, Abu Saleh Md Moin, Thozhukat Sathyapalan, Stephen L. Atkin
Summary: This study compared complement system factors in obese, insulin-resistant PCOS patients with nonobese, non-insulin-resistant PCOS patients. The results showed that the alternative complement pathway was upregulated in both groups, but more pronounced in the obese PCOS group. The upregulation of complement factors was counterbalanced by upregulation of complement inhibitors, suggesting that PCOS may amplify the activation of complement pathways in response to cardiovascular events or infections.
Article
Immunology
Yen-Ling Chiu, Wei-Chou Lin, Kai-Hsiang Shu, Yi-Wen Fang, Fan-Chi Chang, Yu-Hsiang Chou, Ching-Fang Wu, Wen-Chih Chiang, Shuei-Liong Lin, Yung-Ming Chen, Ming-Shiou Wu
Summary: The study found that IgAN patients had higher levels of C5a, factor Ba, and Gd-IgA(1) in plasma compared to healthy controls, with Gd-IgA(1) positively correlated with C5a and factor Ba. Factor Ba and Gd-IgA(1) levels were positively associated with proteinuria, and negatively associated with renal function. Immunosuppressive therapy significantly reduced plasma levels of C5a, factor Ba, and Gd-IgA(1) in patients, leading to decreased proteinuria and stable renal function.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Zi-jun Sun, Dong-yuan Chang, Min Chen, Ming-hui Zhao
Summary: Accumulating evidence suggests the pathogenic role of immunity and metabolism in diabetic kidney disease (DKD). In this study, the researchers investigated the effect of complement factor B (CFB) on lipid metabolism in the development of DKD. They found that CFB deficiency inhibited activation of the complement alternative pathway and attenuated kidney damage in DKD, especially tubulointerstitial injury, by inhibiting the NF-KB signaling pathway, further blocking the transcription of ceramide synthases (CERS), which regulates the biosynthesis of ceramide. CFB may be a promising therapeutic target of DKD.
Article
Immunology
Alexandra T. T. Matola, Angela Fulop, Bernadette Rojkovich, Gyorgy Nagy, Gabriella Sarmay, Mihaly Jozsi, Barbara Uzonyi
Summary: This study analyzed the presence and role of autoantibodies against complement proteins in Hungarian rheumatoid arthritis (RA) patients. Autoantibodies against C1q, MBL, and FB were detected in a small number of patients and were found to have inhibitory effects on complement function. These results support the involvement of the complement system in the pathomechanism of RA and suggest the presence of protective autoantibodies against the alternative pathway C3 convertase in some patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Dian-Chun Shi, Shao-Zhen Feng, Zhong Zhong, Lu Cai, Meng Wang, Dong-Ying Fu, Xue-Qing Yu, Ming Li
Summary: The rs12614 mutation in the CFB gene is associated with a decreased risk of IgAN, possibly by attenuating AP activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sigridur Sunna Aradottir, Ann-Charlotte Kristoffersson, Lubka T. Roumenina, Anna Bjerre, Pavlos Kashioulis, Runolfur Palsson, Diana Karpman
Summary: The study indicates that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.
FRONTIERS IN IMMUNOLOGY
(2021)
Letter
Cardiac & Cardiovascular Systems
Matthew Lukies, Helen Kavnoudias, Adil Zia, Robin Lee, Julian J. Bosco, Tim Joseph, Warren Clements
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
(2021)
Review
Immunology
Emily S. J. Edwards, Julian J. Bosco, Samar Ojaimi, Robyn E. O'Hehir, Menno C. van Zelm
Summary: Predominantly antibody deficiency (PAD) is a common form of primary immunodeficiency characterized by clinical, immunological, and genetic heterogeneity. While some pathogenic gene variants have been identified, many genes remain unknown, prompting the need for a multidisciplinary approach to improve diagnosis and treatment outcomes for PAD. Late onset of disease presentation and the potential influence of genetic and non-genetic factors further highlight the complexity of PAD pathogenesis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Ophthalmology
Nicole K. Kelly, Aheli Chattopadhyay, S. R. Rathinam, John A. Gonzales, Radhika Thundikandy, Anuradha Kanakath, S. Bala Murugan, R. Vedhanayaki, Dean Cugley, Lyndell L. Lim, Eric B. Suhler, Hassan A. Al-Dhibi, Caleb D. Ebert, Elyse J. Berlinberg, Travis C. Porco, Nisha R. Acharya
Summary: The study evaluated changes in health-related and vision-related quality of life among patients with noninfectious uveitis treated with antimetabolites. The results showed that patients in the treatment group had significant improvements in VRQoL and HRQoL over the course of 1 year, indicating a positive impact on their overall well-being and daily functioning.
Letter
Hematology
Akira Nishimura, Takuya Naruto, Satoshi Miyamoto, Andrew Grigg, Julian J. Bosco, Akihiro Hoshino, Keishiro Amano, Shotaro Iwamoto, Masahiro Hirayama, Masahiro Migita, Osamu Ohara, Masatoshi Takagi, Tomohiro Morio, Menno C. van Zelm, Hirokazu Kanegane
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Immunology
R. Ameratunga, A. Jordan, A. Cavadino, S. Ameratunga, T. Hills, R. Steele, M. Hurst, B. McGettigan, I Chua, M. Brewerton, N. Kennedy, W. Koopmans, Y. Ahn, R. Barker, C. Allan, P. Storey, C. Slade, A. Baker, L. Huang, S-T Woon
Summary: Common variable immunodeficiency disorders (CVID) are multi-system disorders characterized by target organ damage mediated by infective, autoimmune, and inflammatory processes. Bronchiectasis is a common disabling complication of CVID, with risk factors including early-onset disease, diagnostic delay, and increased infections. This study found that patients with bronchiectasis have a higher mortality rate, likely due to more severe infections associated with early disease onset and delayed diagnosis.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Editorial Material
Dermatology
I. M. Winship, D. Bajwa, N. Rajan
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
B. A. Thompson, K. Dear, E. Donaldson, R. Nixon, I. M. Winship
Summary: The clear segregation of the TRPM3 variant in the clinical investigation of a family with debilitating centrofacial pruritus by exome sequencing strongly suggests a causal relationship.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Review
Critical Care Medicine
Samuel J. Slater, Matthew Lukies, Helen Kavnoudias, Adil Zia, Robin Lee, Julian J. Bosco, Tim Joseph, Warren Clements
Summary: The spleen is commonly injured in blunt abdominal trauma, and splenic artery embolization (SAE) is a mainstay treatment for stable patients. Splenectomy is the main treatment for unstable patients. The spleen plays an important role in immune function, but splenectomy impairs immune function and increases susceptibility to infection. SAE may preserve immune function. This review discusses the literature on immune function following different treatments for blunt splenic injury and the controversy surrounding quantifying splenic immune function.
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
(2022)
Article
Medicine, General & Internal
Josh Chatelier, Stephanie Stojanovic, Tiffany Lin, Eve Denton, Eli Dabscheck, Mark Hew, Julian J. Bosco
Summary: This study found that males, older patients, and those triggered by insect sting or unknown cause were more likely to require repeated adrenaline administration. Therefore, it is recommended that all anaphylaxis patients carry two adrenaline auto-injectors.
INTERNAL MEDICINE JOURNAL
(2021)
Article
Immunology
Samantha Chan, Jack Godsell, Miles Horton, Anthony Farchione, Lauren J. Howson, Mai Margetts, Celina Jin, Josh Chatelier, Michelle Yong, Joseph Sasadeusz, Jo A. Douglass, Charlotte A. Slade, Vanessa L. Bryant
Summary: This study reveals the association between CMV infection and CVID, as well as the impact of CMV infection on morbidity and mortality in CVID patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Allergy
Joseph Francis De Luca, Graham Angus Mackay, Josh William Chatelier, Samantha Sing-Yi Chan, Stephanie Sihan Zhang, Jack Godsell, Kymble Spriggs, Charlotte Slade, Jo Anne Douglass
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Genetics & Heredity
Joanne Isbister, Adrienne Sexton, Laura E. Forrest, Paul James, James Dowty, Jessica Taylor, Jehannine Austin, Ingrid Winship
Summary: Genetic counseling plays a critical role in supporting individuals and their families in adapting to psychiatric conditions. However, little data exists on the practice and attitudes of Australian genetic counselors regarding psychiatric genetic counseling (PGC). This survey found that most Australian genetic counselors do not specialize in psychiatric genetics and rarely see patients with a personal or family history of psychiatric disorders. While more than half of respondents believed there was sufficient evidence to support PGC, only a minority provided genetic counseling on this topic. Most respondents lacked confidence in providing risk assessments for psychiatric disorders but expressed interest in specialist training and incorporating PGC into their future practice.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Oncology
Sowmya Jonnagadla, Sharelle L. Joseland, Sibel Saya, Nicole den Elzen, Joanne Isbister, Ingrid M. Winship, Daniel D. Buchanan
Summary: This qualitative study explored the psychosocial and behavioral responses of endometrial cancer patients receiving a suspected Lynch syndrome diagnosis. The results showed that patients who interpreted their result as negative for Lynch syndrome believed they were at population-level risk of cancer and felt happy and relieved, while those who interpreted their result as inconclusive experienced confusion and negative emotions. Most patients adhered to colorectal cancer screening recommendations and communicated their genetic test result to family members, but communication of family cancer risk management advice was limited. A family history of cancer and healthcare background influenced patients' engagement in regular cancer screening.
HEREDITARY CANCER IN CLINICAL PRACTICE
(2022)
Article
Oncology
Nicole den Elzen, Sharelle L. Joseland, Sibel Saya, Sowmya Jonnagadla, Joanne Isbister, Ingrid Winship, Daniel D. Buchanan
Summary: Our study findings suggest that there is variability in patients' interpretations of their SLS diagnosis, cancer risk management, and family communication. Despite the uncertainty, almost all participants adhered to cancer risk management advice, although different participants received different advice. All participants also communicated any cancer risk management advice to first-degree relatives to protect them, but the information communicated was not always consistent with the advice received.
HEREDITARY CANCER IN CLINICAL PRACTICE
(2021)
Article
Oncology
Mark A. Jenkins, Daniel D. Buchanan, John Lai, Enes Makalic, Gillian S. Dite, Aung K. Win, Mark Clendenning, Ingrid M. Winship, Richard B. Hayes, Jeroen R. Huyghe, Ulrike Peters, Steven Gallinger, Loic Le Marchand, Jane C. Figueiredo, Rish K. Pai, Polly A. Newcomb, James M. Church, Graham Casey, John L. Hopper
Summary: Polygenic risk scores (PRS) that predict colorectal cancer in the general population do not predict colorectal cancer for individuals with Lynch syndrome, as revealed by a study on 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes.
JNCI CANCER SPECTRUM
(2021)
