Are Chinese aHUS Patients different?

Article No 385

7 October 2020

Apart from wanting to know  how many ( prevalence of ) aHUS patients there are in their country,  another question asked by aHUS patients is how to do they differ.

A country like China has a massive population, 1. 4 billion people, not quite a fifth of the world’s population. so quite a  substantial number.

If aHUS patients there had the same treatment as in more developed countries like the USA there could be around 14000 aHUS patients now living there. But it doesn’t have such healthcare, and those with rare disease are only just beginning to been seen as people facing inequity in healthcare.
However, there could still be  about 1400 aHUS patients in China  if prevalence rates are at the other end of the spectrum.
More likely the number is between the upper and lower estimates , probably around 5000  because patients there may be able to access dialysis and plasma exchange. So maybe more than the estimated 3500 in the USA.
So what may be different about them?
aHUS Global Action was surprised to come across an article written in 2016 which analysed the characteristics of a small number of Chinese aHUS patients.
Led by Dr Hulmei Chen , the group studied the characteristics of 23 Chinese aHUS patients  to learn more about aHUS in China and to see if  there were any differences with other parts of the world. A full copy of their study can be  read here.
The 23 patients were recruited from the Renal Disease Biobank of Jinling Hospital. The 23  patients had renal biopsies between 2000 and 2012 and had been given an aHUS diagnosis. The patients agreed to participate in the study. All of them had been treated with immunosuppressants and plasma exchange. All patients were still being followed up in 2014.
Genetic testing was performed using the variant/mutation  panel for CFH, CFI , MCP etc. The number of results was high but with subsequent analysis including using Sanger Sequencing, aHUS causative variants were identified and catergorised into disease related mutations, novel mutations and “rare” polymorphisms.
All patients were of Han descent i.e. the highest ethnic group in China. The mean age of the patients just less that 36  years old . There were 10 men, (40%) and 13 women. All patients had acute renal failure on presentation and microangiopathic hemolytic anemia. Just under 70 % had thrombocytopenia. Their kidneys had signs of clotting and TMA , and schistocytes (red blood cell fragments) were apparent in their blood. No family history of aHUS ,or kidney failure, was reported. So all were sporadic cases. 12 had  recovered renal function.
The mutations were found in 12 patients out of the 23 patients.The article reports on the specific mutation found for each of these patient. 4 patients had more than one mutation.  So aHUS susceptibility factors were seen in over 52% of the patients, and 48% were idiopathic. Something that would not be unusual in western aHUS populations.
Although acknowledging that the low numbers of the Chines cohort might not  make comparisons valid, the group compared the individual complement component mutations with patients from USA , Europe and  Japan using the same mutation panel as each of the comparator nation. Results from the Alexion aHUS Registry have been added by Global Action though its figures are based on variable screening panels per individual Complement component .Global Action also has added its findings on the complement mutations undertaken in its 2016 Global Poll. The results  are given in the Table 1 below.
Table 1.  Comparison of aHUS patients’ Complement component mutations.

China  USA Japan  Europe  Alexion Registry Global Action
Cohort No. 23 144 10 795 851 223*
% with mutation 52 45.8 80.0 40.6 Variable** 52
Individual Component % % % % % %
C3 8.7 2.1 50.0 5.7 6.0 5.8
MCP 17.4 4.9 20.0 8.2 9.0 4.3
CFB 13.0 4.2 1.1 2.0 3.0
CFH 13.0 27.1 20.0 19.9 21.0 25.3
CFI 4.3 8.3 5.8 6.0 6.4
CFHR (2,3,5) 13.0 2.8 NR NR 6.0
THBD 4.4 2.8 10.0 NR NR 4.3

*43% of respondents from USA and 57%  from 22 countries in the rest of the world
** depends on number of patients screened for each component in the mutation panel.
Chinese aHUS patients have relatively higher levels of C3 mutations, except for Japan. This may be indicative of a SE Asian trait. Similarly Chinese patients have more  MCP, CFB and CFHR mutations. But there are markedly less  of  the more common CFH mutations  that are seen in USA and European aHUS populations.
The differences may have an impact on disease prognosis and management. Chinese aHUS patients  are relatively more exposed to aHUS because of the  higher risk susceptibility factors  C3, CFB and CHFR ,rather than CFH, which is much more common in  aHUS patients in the west. CFHR rearrangements are also highly associated with Anti-FactorH antibody TMA. But  Chinese aHUS patients could well benefit from the lower risks that MCP mutations presents in remission ,kidney transplants and complement inhibitor withdrawal.
As all cases were reported as sporadic i.e. non familial, it is unlikely that any aHUS patient of Chinese descent elsewhere in the world will have identical  mutations.
The research group also made some observations on outcomes after 90 months for those with known susceptibility factors and those without. Those who were susceptible had a higher rates of remission ( 50% v 23%)  and renal recovery (58% v 45%) after first onset. But in follow up none of those with a CFH mutation were in remission nor had renal function; whereas those with MCP mutations  50 % were in remission and 75% had retained kidney function.
The group concluded that “the sample size might lead to analysis bias and reduce the significance of the findings”.  That may well be but at least some evidence exists.
aHUS is one of the 121 rare diseases that the Chinese Government has listed for attention as a disease with an unmet need for effective  treatment in China though such treatments exist ( Global Action reported on this  for Rare Diseases Day 2020,  see Article 324  )
That article also reports that a new biosimilar to eculizumab is being developed by Samsung Biosepsis and  is to be trialed in China, offering hope for those Chinese aHUS patients who would need it for as long as they need it.

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