IgM, IgG
and IgA PDN.

but there are actually 2 sets.

1. Anti-MAG IgM PDN. Evidence exists to support the view that at least 50% of IgM PDN's are a fairly distinctive sub- group. The suspicion that the anti-nerve antibodies that are a component of a paraprotein are responsible for neural damage has been confirmed in findings about the responsibility of the IgM paraprotein of this sub-set of the neuropathy. The paraprotein recognises another protein on the myelin sheath of the nerve cells, a minor protein component of nerve known as Myelin-Associated Glycoprotein - MAG - and it then reacts. It binds specifically to this part of the nerve myelin and, it is postulated, causes the damage to the myelin insulation and sometimes to the axons. So this chronic neuropathy has been triggered. This sub-set is thus known as anti-MAG IgM neuropathy . IgM anti-MAG sufferers have a mainly sensory disorder and a low response to treatment.

2. Non anti-MAG IgM’s. With the other 50% of IgM PDN no detectable antibody activity (pathogenesis) has yet been identified. They are closely similar to the IgG and IgA PDN.

Overall in IgM PDN's the damage may be mixed motor and sensory but in some 80% of cases – typically anti-MAG - it is predominantly sensory, but predominantly motor in the rest. Most cases follow a slow course of progress, the majority of the cases being in men. There is often numbness, tingling, muscle weakness, upper limb tremor, ataxia (loss of control of bodily movements including imbalance) and unsteady gait amongst anti-MAG IgM PDN sufferers.

THE IgG PDN IS LESS COMMON. EVEN LESS FREQUENT ARE IgA PDN's . The anti-nerve antibody cause/effect relationship (pathogenesis) in IgG and IgA PDN is, at present, less understood than with the anti-MAG IgM PDN. The IgG and IgA PDN's have a more considerable overlap with or resemblance to CIDP in their clinical picture than the IgM PDN's. They may be solely demyelinating or have mixed demyelinating and axonal features. They are usually less disabled than IgM sufferers. Most are chronic and slowly progressive sensory/motor in their nature. Some have a remitting, relapsing course.

IgA PDN. It was only in 1986 that Bailey et al. described the first case in which benign monoclonal IgA gammopathy was associated with polyneuropathy. Sural nerve biopsy had revealed axonal loss and myelin changes. Simmons et al (1993) describe IgA cases as having painful parasthesia, sometimes burning, sensory loss and/or weakness. Some IgA PDN patients can show features similar to anti-MAG IgM PDN. IgA PDN cases in special studies by specialist neurologists are usually too few for there to be any meaningful analysis in comparison with IgM and IgG.


In a series of 62 cases reported by Yeung et al (1991), 46 were IgM, 11 were IgG and 5 IgA. Gosselin et al (1991) reported on 65 cases of PDN or MGUS neuropathy. 31 were IgM, 24 were IgG and 10 IgA. In a study of 42 consecutive patients with MGUS-associated neuropathy by Morris A Palmer and John R Wilson (1995-1999) 12 patients were IgM, 25 were IgG and 5 were IgA. The youngest age of onset in a series of cases reported by Yeung et al (1981) was 28 years. It is rare below 40. Simmons et al say that there is no great difference between the 3 groups. Yet L Magy et al (Nov 2003), in a study of 55 patients, 40 IgM and 15 IgG or IgA , state that several features allowed them to distinguish between the 2 groups. 75% of the IgM cases had a predominantly sensory clinical picture compared with 27% of the IgG/IgA cases. The demyelinating pattern was more heterogeneous (dissimilar in kind) in IgG/IgA than in IgM. There were other clinical and electrophysiological differences.

Differences between PDN and CIDP . Although L Magy et al describe the IgG/IgA neuropathies as similar to classic CIDP:-

  1. Impairment generally develops more slowly in PDN than in CIDP, with a longer period from onset to main impairment.

  2. There is less severe functional impairment and muscle weakness than in CIDP.

  3. PDN sufferers experience a greater severity of sensory loss and more numbness than CIDP sufferers.

  4. They also experience a smaller degree of improvement than CIDP patients (Simmons et al.). Prof Hugh Willison has said (2001) that in these PDNs the damage is usually there forever and it tends to be a long-term illness.

It should be noted that 20% to 25% of CIDP patients also have a paraprotein present in their serum but the meaning of the association is unclear! So it can be difficult to differentiate between CIDP and PDN.

AN AXONAL VARIETY. K C Gorson and A H Ropper (1997) in a study of 16 MGUS/paraprotein patients with pure or predominantly axonal neuropathy conclude that there is a paraproteinaemic axonal neuropathy that is clinically and electrophysiologically distinct from the more unusual demyelinating pattern. 12 of them were IgG, 3 were IgM and one was IgA. They compared them with 20 patients with the demyelinating form of PDN.

Please note: These notes are based on my experience and my reading of published professional material. They should not be understood as coming from any personal medical expertise. Should anyone, especially a professional neurologist, notice any error please contact me.