OK, so HUS is caused by e.coli toxins and aHUS results from Complement dysregulation. Both are thrombotic microangiopathies.
HUS is more common than aHUS, but not everyone who gets an e.coli viral infection develops HUS.
aHUS has more triggers than HUS, which has an e.coli infection as its sole trigger.
The complement dysregulation in aHUS results from rare genetic defects in Complement components, at least one of which is found in aHUS patients, but not in all patients. Those patients are idiopathic.
Their genetic defect is yet to be found or something else is to be found which HAMPERS perfectly good parts of Complement working properly.
Anti factor H antibodies have been found to stop Complement Factor H, CFH, from working as it should when needed to control Complement from becoming over active.
Then it is learned that HUS can be triggered by more infections than e.coli.
The S.Pneumonia bacteria, for example, can be a trigger. It rarely happens but it can lead to a TMA. That TMA can be classified as an infection TMA like e.coli HUS and is an HUS.
Clinicians say that S.Pneumonia is a worse than e.coli HUS. This is because sepsis, meningitis and pneumonia could be present too. It does not get the same level of recognition, or awareness, as e.coli HUS.
So probably lost somewhere between e.coli HUS and a “secondary” aHUS.
A recent article (see HERE) by the Delgado Group offers a genetic explanation of the way that S. Pneumoniae bacteria HAMPERS good CFH from working properly. Making it a Complement mediated TMA, or an aHUS.
Previous limited research in Hungary had identified S.Pneumoniae HUS patients with rare complement genetic variants and other more common genetic variants, or haplotypes in doctors speak, which put those who are susceptible to an S.Pneumonia aHUS at more risk of it happening.
The Degardo Group studied 13 Spanish S. Pneumonia patients. They found five had rare complement variants of unknown significance. They also also found the frequency of the at risk haplotypes in their CFH, and related components 1 and 3, was similar to those with aHUS.
To understand more about the workings of Complement in an S. Pneumonia infection, the group undertook an experiment with CFH in vitro , and removed a part of the protein, the sialic acid, as they believed this would be done by the bacteria.
When removed, or desialylated, they found that CFH was hampered from working properly.
The Group concluded that this process might have a role in the way the aHUS is triggered.
Such desialylation would only be transitory and once Complement came under control, a remission would be likely.
Increasingly conditions that were not regarded as aHUS are found to have disease mechanisms that are just like aHUS when Complement is hampered.
Each becoming a rare disease within a very rare disease.
A previous website article about S. Pneumoniae can be seen HERE
Article No. 468