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Written by my girlfriend, the old Red Riding Hood editor | XI CHAPLE disease, the full name is CD55 deficiency caused by overactivation of the complement system, thrombosis and protein-losing enteropathy Referred to as CHAPLE).
In fact, it was not until 2017 that people discovered that the overactivation of the complement system and the innate immune system caused by the CD55 gene defect is the culprit of this disease [1,2].
The clinical symptoms include diarrhea, vomiting, abdominal pain, starvation edema, repeated infections, and fatal thrombosis [3].
Understanding the pathology of this disease and mastering the intervention methods of this disease are vital to the survival and development of human beings.
The complement system is composed of a set of proteins, which participate in innate and acquired immune responses, release biologically active polypeptide anaphylactoxins, thereby destroying pathogens, removing apoptotic cells and residual substances [4,5], and CD55 and other cells Surface glycoproteins can protect normal cells such as blood cells, epithelial cells and endocrine cells from the damage of the complement system [6].
It has been reported that the complement C5 inhibitor eculizumab (eculizumab) can effectively alleviate this disease [1, 7].
It can bind to C5 and inhibit its function, while CD55 has a negative regulatory relationship with C5.
Of course, the specific metabolism and immune response that eculizumab can cause is still poorly understood.
Recently, the Ahmet Ozen team from Turkey and the Michael J Lenardo team from the National Institutes of Health published an article titled Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease in Nature Immunology, and found that eculizumab can effectively recover Intestinal metabolism and immune function in patients with CHAPLE disease.
First of all, the author gave 15 patients from Turkey and one from the Netherlands to eculizumab treatment, and found that the effect was very good, basically all patients no longer need hospitalization.
In addition, the intestinal symptoms and edema of these patients were significantly relieved within 4 weeks, the levels of vitamin B12 and serum immunoglobulin were significantly improved, the resistance was significantly improved, the probability of repeated infections was reduced, and the triglycerides, platelets and blood cells were abnormal.
The phenomenon of elevation and aggregation weakened or disappeared, and the structure and function of the digestive tract gradually returned to normal.
Next, the author studied the pharmacokinetics of eculizumab.
The authors found that once a week, eculizumab and free C5 can meet the required standards and exist stably.
Next, the author studied the specific effects of eculizumab on each protein component of the complement system.
The authors found that compared with healthy people, the levels of C3a, C4b, and C5a in patients suffering from CHAPLE have increased, while the level of complement factor H (complement factor H) has decreased.
After receiving eculizumab treatment, the levels of free C5, C5a, sC5b-6 and sC5b-9 have declined, and the level of complement factor H has recovered, but the level of C3a has not changed much.
In general, eculizumab can effectively inhibit the abnormal activation of the complement system in CHAPLE patients.
Finally, the author studied the changes in the intestinal flora and metabolic function of patients after eculizumab treatment.
The author studied the excreta of 6 patients before and after treatment by using macrogenomics research methods, and found that eculizumab is likely to alleviate and eliminate factors that affect the balance of intestinal flora, including intestinal inflammation and intestinal activity.
Abnormalities, abnormal food intake and the influence of antibiotics and other drugs, etc.
, play a role in rebuilding the intestinal flora and maintaining the homeostasis of the flora.
In addition, the author analyzed 1305 serum proteins from 8 patients and found that compared with healthy people, the patients had 26 protein levels decreased and 68 protein levels increased.
After receiving eculizumab treatment, the protein levels of these changes basically tended to be normal.
Among them, one of the most obvious proteins is insulin-like growth factor (IGF) binding protein 2 (IGFBP2), which is involved in metabolism.
In addition, there are some proteins.
Compared with the normal population, the patients did not change significantly, but after treatment with eculizumab, the level increased significantly.
One of the representatives is EPOR, whose main function is to mediate endothelial cell repair.
Based on the above results, it is known that inhibiting C5 in the complement system can effectively improve the immune system and metabolic system abnormalities of CHAPLE patients.
In summary, the authors verified that the C5 inhibitor eculizumab is an excellent method for the treatment of CHAPLE.
Eculizumab can effectively relieve the patient's gastrointestinal symptoms and abnormalities of the immune system and metabolic system.
In addition, the abnormal levels of proteins in the serum can be recalled, and the abnormal intestinal flora can be reconstructed.
Therefore, the inhibition of component C5 of the complement system by eculizumab can regulate the function of the complement system, thereby treating humans due to CD55 deficiency The resulting CHAPLE disease. Original link https://doi.
org/10.
1038/s41590-020-00830-z Platemaker: Qi Jiang Reference [1] Ozen, A.
et al.
CD55 deficiency, early-onsetprotein-losing enteropathy, and thrombosis.
N .
Engl.
J.
Med.
377, 52–61 (2017) [2] Kurolap, A.
et al.
Loss ofCD55 in eculizumab-responsive protein-losing enteropathy.
N.
Engl.
J.
Med.
377,87–89 ( 2017).
[3] Ozen, A.
CHAPLE syndromeuncovers the primary role of complement in a familial form of Waldmann's disease.
Immunol.
Rev.
287, 20–32 (2019).
[4] Mevorach, D.
Clearance of dying cells and systemic lupus erythematosus: the role of C1q and thecomplement system.
Apoptosis 15, 1114–1123 (2010).
[5] Holers, VM Complement and its receptors: new insights into human disease.
Annu Rev.
Immunol.
32, 433–459 (2014) [6] Elvington, M.
, Liszewski, MK & Atkinson, JP Evolution of the complement system:from defense of the single cell to guardian of the intravascular space.
Immunol.
Rev.
274, 9–15(2016).
[7] Waldmann, TA, Steinfeld,JL, Dutcher, TF, Davidson, JD & Gordon, RS Jr.
The role of thegastrointestinal system in'idiopathic hypoproteinemia'.
Gastroenterology 41, 197–207 (1961).
In fact, it was not until 2017 that people discovered that the overactivation of the complement system and the innate immune system caused by the CD55 gene defect is the culprit of this disease [1,2].
The clinical symptoms include diarrhea, vomiting, abdominal pain, starvation edema, repeated infections, and fatal thrombosis [3].
Understanding the pathology of this disease and mastering the intervention methods of this disease are vital to the survival and development of human beings.
The complement system is composed of a set of proteins, which participate in innate and acquired immune responses, release biologically active polypeptide anaphylactoxins, thereby destroying pathogens, removing apoptotic cells and residual substances [4,5], and CD55 and other cells Surface glycoproteins can protect normal cells such as blood cells, epithelial cells and endocrine cells from the damage of the complement system [6].
It has been reported that the complement C5 inhibitor eculizumab (eculizumab) can effectively alleviate this disease [1, 7].
It can bind to C5 and inhibit its function, while CD55 has a negative regulatory relationship with C5.
Of course, the specific metabolism and immune response that eculizumab can cause is still poorly understood.
Recently, the Ahmet Ozen team from Turkey and the Michael J Lenardo team from the National Institutes of Health published an article titled Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease in Nature Immunology, and found that eculizumab can effectively recover Intestinal metabolism and immune function in patients with CHAPLE disease.
First of all, the author gave 15 patients from Turkey and one from the Netherlands to eculizumab treatment, and found that the effect was very good, basically all patients no longer need hospitalization.
In addition, the intestinal symptoms and edema of these patients were significantly relieved within 4 weeks, the levels of vitamin B12 and serum immunoglobulin were significantly improved, the resistance was significantly improved, the probability of repeated infections was reduced, and the triglycerides, platelets and blood cells were abnormal.
The phenomenon of elevation and aggregation weakened or disappeared, and the structure and function of the digestive tract gradually returned to normal.
Next, the author studied the pharmacokinetics of eculizumab.
The authors found that once a week, eculizumab and free C5 can meet the required standards and exist stably.
Next, the author studied the specific effects of eculizumab on each protein component of the complement system.
The authors found that compared with healthy people, the levels of C3a, C4b, and C5a in patients suffering from CHAPLE have increased, while the level of complement factor H (complement factor H) has decreased.
After receiving eculizumab treatment, the levels of free C5, C5a, sC5b-6 and sC5b-9 have declined, and the level of complement factor H has recovered, but the level of C3a has not changed much.
In general, eculizumab can effectively inhibit the abnormal activation of the complement system in CHAPLE patients.
Finally, the author studied the changes in the intestinal flora and metabolic function of patients after eculizumab treatment.
The author studied the excreta of 6 patients before and after treatment by using macrogenomics research methods, and found that eculizumab is likely to alleviate and eliminate factors that affect the balance of intestinal flora, including intestinal inflammation and intestinal activity.
Abnormalities, abnormal food intake and the influence of antibiotics and other drugs, etc.
, play a role in rebuilding the intestinal flora and maintaining the homeostasis of the flora.
In addition, the author analyzed 1305 serum proteins from 8 patients and found that compared with healthy people, the patients had 26 protein levels decreased and 68 protein levels increased.
After receiving eculizumab treatment, the protein levels of these changes basically tended to be normal.
Among them, one of the most obvious proteins is insulin-like growth factor (IGF) binding protein 2 (IGFBP2), which is involved in metabolism.
In addition, there are some proteins.
Compared with the normal population, the patients did not change significantly, but after treatment with eculizumab, the level increased significantly.
One of the representatives is EPOR, whose main function is to mediate endothelial cell repair.
Based on the above results, it is known that inhibiting C5 in the complement system can effectively improve the immune system and metabolic system abnormalities of CHAPLE patients.
In summary, the authors verified that the C5 inhibitor eculizumab is an excellent method for the treatment of CHAPLE.
Eculizumab can effectively relieve the patient's gastrointestinal symptoms and abnormalities of the immune system and metabolic system.
In addition, the abnormal levels of proteins in the serum can be recalled, and the abnormal intestinal flora can be reconstructed.
Therefore, the inhibition of component C5 of the complement system by eculizumab can regulate the function of the complement system, thereby treating humans due to CD55 deficiency The resulting CHAPLE disease. Original link https://doi.
org/10.
1038/s41590-020-00830-z Platemaker: Qi Jiang Reference [1] Ozen, A.
et al.
CD55 deficiency, early-onsetprotein-losing enteropathy, and thrombosis.
N .
Engl.
J.
Med.
377, 52–61 (2017) [2] Kurolap, A.
et al.
Loss ofCD55 in eculizumab-responsive protein-losing enteropathy.
N.
Engl.
J.
Med.
377,87–89 ( 2017).
[3] Ozen, A.
CHAPLE syndromeuncovers the primary role of complement in a familial form of Waldmann's disease.
Immunol.
Rev.
287, 20–32 (2019).
[4] Mevorach, D.
Clearance of dying cells and systemic lupus erythematosus: the role of C1q and thecomplement system.
Apoptosis 15, 1114–1123 (2010).
[5] Holers, VM Complement and its receptors: new insights into human disease.
Annu Rev.
Immunol.
32, 433–459 (2014) [6] Elvington, M.
, Liszewski, MK & Atkinson, JP Evolution of the complement system:from defense of the single cell to guardian of the intravascular space.
Immunol.
Rev.
274, 9–15(2016).
[7] Waldmann, TA, Steinfeld,JL, Dutcher, TF, Davidson, JD & Gordon, RS Jr.
The role of thegastrointestinal system in'idiopathic hypoproteinemia'.
Gastroenterology 41, 197–207 (1961).
