Raising awareness of autoimmune nodopathies

The guest lecture at the Neurology Update Meeting 2024 was provided by Prof Simon Rinaldi, Clinical Director at the Oxford Autoimmune Neurology Diagnostic Laboratory, UK.

Prof Rinaldi’s lecture was titled  ‘Bridging the gap: Dissecting the autoimmune nodopathies’.

The talk covered the history of clinical and experimental data in relation to the area.

It highlighted the relevance of nodal/paranodal antibodies in the differential diagnosis of acute, severe, or atypical inflammatory neuropathies.

Prof Rinaldi stressed that the node is an important target for antibodies in autoimmune neuropathies.

He said the detection of antibodies targeting nodal and paranodal cell-adhesion molecules defines a group of distinct conditions that are important to recognise.

Speaking to the Medical Independent (MI), Prof Rinaldi said work in the field has advanced significantly over the past decade.

“There are now lots of labs doing the testing; there’s lots more information coming through,” he explained.

“And it’s really grown over the past 10 years, expanding the number of antibodies we know about, expanding how much we know about the clinical syndromes, and how they’re treated.”

In his lecture, Prof Rinaldi acknowledged there is a debate about how widespread testing should be and when testing should be conducted. He stressed it should be borne in mind that these conditions are clinically and pathologically different and have a divergent treatment response profile compared to Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy (CIPD).

“I have one opinion, which is if you are going to treat someone for Guillain-Barré syndrome or CIDP, you should probably think about these antibodies and test for them,” he told MI.

“Because if you find them, it’s going to change your thinking about what agents you use and in what order. Other people would say, ‘why don’t you just treat first and then if it doesn’t go as expected, then you test the antibodies.’ And the reason I go against that is one, that you may have spent a lot of money on immunoglobulin that is not going to do anything. And two, you may have made those tests more difficult to interpret, if you have already started treatment before you do them.”

Prof Rinaldi described autoimmune nodopathies as “treatable disorders”, with rituximab being “the most sustained and overall effective” medication.

“On the other side of that, recovery is actually about the ability of the peripheral nervous system to regenerate and repair,” he told this newspaper.

“Probably the earlier you can get in and turn off the damaging process the more chance there is of a full recovery. But, actually, some of those deficits can become potentially permanent if they are long-standing, if they are severe. I think that’s again why early diagnosis is potentially important. Because if you can stop this process before lots of damage accrues, outcomes, I think, will be better.”

In terms of future directions, Prof Rinaldi said research is being conducted to further refine the individual syndromes, which have their distinct characteristics.

For example, IgG1 pan-neurofascin antibodies are associated with a particularly severe form of autoimmune neuropathy. Patients typically present with acute, immobilising sensorimotor neuropathy, accompanied by cranial nerve involvement and long-term respiratory insufficiency. In the chronic phase of the disease, antibodies targeting nodal and paranodal proteins are predominantly of the IgG4 subclass.

“So those pan-neurofascin patients probably have a distinct pathological process… compared to the rest, with IgG4,” he explained.

“And there may also be different origins in terms of the B cells responsible.”

He said work is required in examining both the ‘induction phase’ and the ‘effector phase’.

“We are trying to refine the immunology of the induction phase: Where do the antibodies come from, why do patients develop them. Then think about the effector end and what are the antibodies doing. Targeting the effector end is probably targeting more of the acute side of things, let’s stop this as quickly as possible. Targeting the induction phase is more about sustained remission and sustained response, and I think we need to address both of those in parallel.”