Uncharacterised Patterns

During screening for paraneoplastic antibodies, it is likely that a number of unusual patterns may be seen on cerebellum. Some of these may be due to non specific cross reaction with other antibodies such as ANA, where as others seen will be of uncertain clinical significance. Here we present some examples of these patterns and hopefully in time clinical relevance may be realised.


Non-Ma nucleolar antibody

This rare nucleolar antibody which reacts with cerebellar neurones and closely resembles Ma2 pattern. Extensive testing did not show any reactivity against stomach, kidney, liver, ovary, testis and ANA. Granular staining in the cytoplasm of HEp2 resembled ribosomal antibody but this was not ribosomal P. This antibody also reacted with peripheral neurones of the stomach but was negative for all the characterised paraneoplastic antibodies. The serum also tested negative against AChR, RF, ENAS, ANCA and TTG.

Patients details: A 58 year old male admitted to intensive care with few weeks history of generalised severe muscle weakness (unable to walk) and aches. Also unable to swallow. Patient died shortly after admission.

Postmortem: Non neurological causes.

Conclusion: This is a rare antibody of undetermined significance which reacts with epitopes of primate liver and cerebellum.

Purkinje cell cytoplasm antibody (Yo/Tr type staining)

Human IgG autoantibody to primate cerebellum. This type of distribution can be mistaken for Yo antibody. The peripheral neurones were also spared.


Western blot rules out the presence of Yo antibody. This antibody binds to a 35kDa protein in the central nervous system.

Purkinje cell cytoplasm antibody (non-Yo type)

Coarse speckled cytoplasmic staining of the Purkinje cells (similar to Yo staining but speckles are very large). In the granular layer (GL), the staining resembles that of Golgi pattern as seen on HEp-2 cells.


Higher magnification showing Golgi type staining pattern in the granular layer and large speckles in the Purkinje cells.



The antibody binds to the molecular layer neurones resembling Golgi like pattern (arrow). A positive dendrite radiating from the neurone is also evident.
Western blot was negative for characterised paraneoplastic neurological antibodies. Weak Golgi staining was seen on HEp-2 cells.

Clinical details:
This serum is from a 70 year old female with a 5 year history of slow progressive cerebellar syndrome affecting gait. MRI scan shows mild generalised atrophy. There were no signs of ovarian tumour. Paraneoplastic cerebellar degeneration is ruled out in view of such long history.

Neuronal nuclei rim

Primate cerebellum showing human IgG binding to the rims of the neuronal nuclei of the Purkinje layer (G is the granular and M is the molecular layer).

Clinical significance: Unknown.

Molecular layer specific antibody

Primate cerebellum showing intense staining of neuronal nuclei (arrows) in the molecular layer (ML). There is no substantial staining of the Purkinje cells (PC) or granular layer (GL) neurones.


At a higher magnification, generalised speckled staining of the molecular layer appears similar to that seen with amphiphysin, The neuronal nuclei (NN) give the impression of being masked with the speckled staining.

On the Western blot there were no bands seen. This sample had homogenous pattern on the HEp-2 cells. Anti-nuclear antibody usually cross reacts with all the neuronal nuclei.

Clinical details:
This is a 67 year old female with peripheral neuropathy and her serum has shown a similar pattern over the last three years.

The example below demonstrates an unusual situation where the paraneoplastic neurological antibody can be masked by a high titre tissue specific antibody (in this case, anti-mitochondrial antibody). 

Masking of Hu by anti-mitochondrial antibodies

This is an example of mitochondrial antibody masking Hu (ANNA1) reactivity that was only revealed when testing by Western blot. It is important to eliminate other antibodies particularly when there is excessive staining as seen here.


Patient details: A 71 year old female diagnosed with primary biliary cirrhosis / sclerosing cholangitis developed subacute onset of patchy sensory neuropathy and autonomic neuropathy. She had a strong anti-mitochondrial antibody which was masking the Hu-antibody.

Western blot: Hu antibody binds to 38 kDa band and recombinant protein.

Unusual patterns produced by IgM and IgG

White matter staining produced by IgG on primate cerebellum

IgG binding to the white (W) matter resembles MAG distribution on cerebellum.. Note both the granular layer (G) and the molecular layer (M) show lack of staining. Clinical significance undetermined.


Unusual IgM staining of primate nerve.

This type of distribution can be easily mistaken for MAG antibody. The serum is from a 57 year old female with IgM kappa paraproteinaemia and IgM Sulphatides at a very high titre. The staining seen is likely to be anti-sulphatides antibodies.


IgM binding to 52, 109 and 132 kDa cerebellar proteins.

Anti-sarcolemma antibody

Human IgG antibody to primate skeletal muscle showing staining of the sarcolemma. This is of undetermined clinical significance. Compare this pattern with striational antibody and cardiac antifibrillary antibody.