Influence of Depleted Complement Activity on the Development of Zymosan-Induced Arthritis

Background: The complement system usually helps protect against microbial infection, but it could also be involved in the onset of various diseases. Inhibition of complement component 5 (C5) with eculizumab has resulted in a significant reduction of hemolysis, reduction of thromboembolic events, and increased survival in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). However, eculizumab requires frequent intravenous infusions due to the abundance of C5 in plasma and some patients may still experience breakthrough hemolysis. This review introduces the recent body of knowledge on recycling technology and discusses the likely therapeutic benefits of SKY59, a novel recycling antibody, for PNH and complement-mediated disorders. Methods: By using recycling technology, we created a novel anti-C5 antibody, SKY59, capable of binding to C5 pH-dependently. Results: In cynomolgus monkeys, SKY59 robustly inhibited C5 and complement activity for significantly longer than a conventional antibody. SKY59 also showed an inhibitory effect on C5 variant p.Arg885His, whereas eculizumab does not suppress complement activity in patients with this type of mutation. Conclusion: SKY59 is a promising anti-C5 biologic agent that has significant advantages over current therapies such as long duration of action and efficacy against C5 variants.

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A 44-kb deleted-type copy number variation is associated with decreasing complement component activity and calf mortality in Japanese Black cattle

BMC Genomics ◽

10.1186/s12864-021-07415-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shinji Sasaki ◽

Youko Miki ◽

Takayuki Ibi ◽

Hiroyuki Wakaguri ◽

Yuichi Yoshida ◽

...

Keyword(s):

Infectious Disease ◽

Copy Number Variation ◽

Copy Number ◽

Risk Allele ◽

Wild Type ◽

Japanese Black Cattle ◽

Complement Activity ◽

Categorical Trait ◽

Number Variation ◽

Calf Mortality

Abstract Background Calf mortality generally occurs in calves prior to weaning, which is a serious problem in cattle breeding. Several causative variants of monogenic Mendelian disorders in calf mortality have been identified, whereas genetic factors affecting the susceptibility of calves to death are not well known. To identify variants associated with calf mortality in Japanese Black cattle, we evaluated calf mortality as a categorical trait with a threshold model and performed a genome-wide copy number variation (CNV) association study on calf mortality. Results We identified a 44-kb deleted-type CNV ranging from 103,317,687 to 103,361,802 bp on chromosome 5, which was associated with the mortality of 1–180-day-old calves. The CNV harbored C1RL, a pseudogene, and an IncRNA localized in the C1R and C1S gene cluster, which is a component of the classical complement activation pathway for immune complexes for infectious pathogens. The average complement activity in CNVR_221 homozygotes at postnatal day 7 was significantly lower than that of wild-type animals and heterozygotes. The frequency of the risk allele in dead calves suffering from diarrhea and pneumonia and in healthy cows was 0.35 and 0.28, respectively (odds ratio = 2.2, P = 0.016), suggesting that CNVR_221 was associated with the mortality of Japanese Black calves suffering from an infectious disease. Conclusions This study identified a deleted-type CNV associated with the mortality of 1–180-day-old calves. The complement activity in CNVR_221 homozygotes was significantly lower than that in heterozygotes and wild type animals. The frequency of the risk allele was higher in dead calves suffering from an infectious disease than in healthy cows. These results suggest that the existence of CNVR_221 in calves could be attributed to a reduction in complement activity, which in turn leads to susceptibility to infections. Thus, the risk allele could serve as a useful marker to reduce the mortality of infected Japanese Black calves.

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Moraxella lacunata infection accompanied by acute glomerulonephritis

Open Medicine ◽

10.1515/med-2020-0234 ◽

2020 ◽

Vol 15 (1) ◽

pp. 962-967

Author(s):

Nami Sawada ◽

Tamaki Morohashi ◽

Tomokazu Mutoh ◽

Tsukasa Kuwana ◽

Junko Yamaguchi ◽

...

Keyword(s):

Clinical Laboratory ◽

Case Reports ◽

Laboratory Data ◽

Inflammatory Cells ◽

Final Diagnosis ◽

Renal Tissue ◽

Acute Glomerulonephritis ◽

Pathological Findings ◽

Complement Activity ◽

Moraxella Lacunata

AbstractMoraxella lacunata (M. lacunata) is a Gram-negative bacterium, which rarely causes serious infection. This is a rare case report of acute glomerulonephritis diagnosed by pathological findings in a child accompanied by M. lacunata infection. The patient showed hematuria, proteinuria and hyperkalemia requiring emergency hemodialysis. After hospitalization, M. lacunata bacteremia became apparent. Pathological findings showed an increase in glomerulus inflammatory cells and glomerular C3 deposition was observed in the renal tissue biopsy. Final diagnosis was endocapillary proliferative glomerulonephritis. Clinical reports of M. lacunata infection requiring emergency hemodialysis in children are rare. Previous reports have suggested that lowered immune competency with chronic kidney disease may be a risk factor associated with serious invasive cases of M. lacunata infection. However, detailed clinical laboratory data and pathological findings have not been identified in previous case reports. Our case directly indicated complement activity and acute glomerulonephritis with M. lacunata infection. Although there are various causes for acute glomerulonephritis, infection-related glomerulonephritis (IRGN) is an important concept. M. lacunata infection might have a potential risk for IRGN with dysregulation of complement activity leading to serious and invasive clinical conditions than previously considered.

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Intravenous and standard immune serum globulin preparations interfere with uptake of 125I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(85)90027-3 ◽

1985 ◽

Vol 34 (2) ◽

pp. 227-236 ◽

Cited By ~ 20

Author(s):

Melvin Berger ◽

Pnina Rosenkranz ◽

Carmen Y. Brown

Keyword(s):

Immune Serum ◽

Immune Serum Globulin ◽

Serum Globulin ◽

Complement Activity ◽

Hemolytic Complement Activity

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PARALLEL STUDIES OF COMPLEMENT AND COAGULATION IV. EFFECT OF CARBON TETRACHLORIDE

Canadian Journal of Medical Sciences ◽

10.1139/cjms51-006 ◽

1951 ◽

Vol 29 (2) ◽

pp. 48-58

Author(s):

Christine E. Rice ◽

Paul Boulanger ◽

P. J. G. Plummer

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Serum Protein ◽

Guinea Pigs ◽

Fatty Degeneration ◽

Blood Groups ◽

Total Serum Protein ◽

Total Serum ◽

Coagulation Time ◽

Complement Activity

To determine whether liver injury would result in a parallel decline in the complement titer and coagulative properties of the blood, groups of guinea pigs were given series of injections of the liver poison, carbon tetrachloride. Marked fatty degeneration of the liver, a decline in total serum protein and albumin, a decrease in complement activity, and a prolongation of coagulation time was observed in the treated animals. A general relationship was noted between the albumin-globulin ratio and the complement titer of the serum and between the complement titer and the coagulation time of the plasma.

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