C4A

Background

Human C4a is a cationic polypeptide that can be directly isolated from fresh serum after the activation of the complement cascade. The C4a anaphylatoxin consists of 77 residues without histidine, tryptophan, and carbohydrate side chains, weighing 8,759 Da. C4a is homologous to C3a and C5a (two anaphylatoxins released by complement activation) in sequence and structure within or between species. During the activation of the complement classical pathway and the lectin pathway, the alpha-chain of the complement component 4 (C4) is respectively cleaved by activated C1s and MASP-2, releasing a small fragment C4a and a large fragment C4b. The C4b is involved in the next step of the complement pathways in the formation of convertases. C4a serves as an anaphylatoxin implicated in inflammatory reactions.

Although similar in structure to other anaphylatoxins, the functional properties of C4a are different from C3a and C5a. Firstly, C4a has no specific receptor and seems to function through the C3a receptor. Secondly, C4a is an anaphylatoxin local inflammation, induces smooth muscle contraction, increases vascular permeability, and causes the release of histamine by mast cells and basophilic leukocytes, but these induced bio-functions are much weaker compared to C3a and C5a. Besides, C4a, as well as C3a, exhibit antibacterial activity against both Gram-negative and Gram-positive bacteria, which is independent of the receptor but depends on the net charge, the proportion of hydrophobic amino acids, and the amphiphilic peptide. It is indicated that the deficiency of the C4a might result in systemic lupus erythematosus and type I diabetes mellitus, and excess was associated with schizophrenia and psychotic bipolar disorder.

Fig.1 C4A structure.Distributed under CC BY-SA 4.0, from Wiki, without modification.

C4A Functional Service

Creative Biolabs provides a wide array of C4A-focused products, such as anti-C4A antibodies, aptamers, ELISA kits, recombinant C4A proteins, and human C4A clone vectors. These tools are designed for effective detection and analysis of interactions involving antibody regions and C4A, playing a vital role in research that aims to develop therapeutic strategies for multiple medical conditions.

Fig.2 Quantification of serum ITIH4, C3, C4A, and TUBB levels in the validation cohort using ELISA analysis.¹

In the quest for objective biomarkers of depression, researchers conducted proteomic analysis on serum from 48 depressive patients and 48 healthy controls. Utilizing magnetic bead-based weak cation exchange and MALDI-TOF-MS, differential protein peaks were screened and analyzed with LC-MS/MS. Five potential markers were identified: Tubulin beta chain, ITIH4, complement component 3, and complement C4A. ELISA validation confirmed their elevated expression in depressive individuals. Logistic regression highlighted these proteins as significant, independent predictors of depression, suggesting their potential as biomarkers for early diagnosis, enabling targeted therapeutic interventions.

Creative Biolabs provides an extensive array of bespoke services centered around C4A, encompassing detailed interaction analyses and various expert evaluations. These meticulously designed services aim to support clients in advancing their scientific research and clinical endeavors.

Reference

1. Guo, Aihong, et al. "Serum proteomic analysis uncovers novel serum biomarkers for depression." Frontiers in Psychiatry 15 (2024): 1346151. Distributed under Open Access license CC BY 4.0, without modification.