JNNP: Validation of MATCH scores, a predictive tool for identifying patients with KELCH-like protein-11 antibodies

Kelch-like protein 11 (KLHL11)-IgG is a high-risk paraneoplastic antibody
associated with rhombosis.
The clinical spectrum associated with KLHL11 IgG paraneoplastic autoimmunity has been expanded
.
However, in most cases of KLHL11 IgG seropositivity, there are some core nerve features
.
Vogrig et al.
proposed a MATCH score that could be used to identify patients
carrying KLHL11 IgG.
The MATCH score consists of five elements: M (male, 1 point), A (ataxia or other cerebellar symptoms, 1 point), T and C (2 points for testicular tumors or other types of tumors), H (hearing impairment, 1 point
).
The authors further clarify that ataxia may also include other forms of cerebellar dysfunction, including nystagmus, intention tremor, and tracking impairment
.
Testicular tumors also include spontaneously degenerative germ cell tumors found in mediastinal lymph nodes and metastatic testicular germ cell tumors
.
Hearing loss includes sensorineural hearing loss or tinnitus
.
The score was tested in a group of patients, including 138 with
suspected paraneoplastic neurological syndrome (PNS).
Using MATCH scores cut-off ≥ 4 points, KLHL11IgG seropositivity has a sensitivity and specificity of 78% and 99%,
respectively.
In this study, the aim was to independently verify MATCH scores
using the PNS database.
This article was published in the Journal of Neurology, Neurosurgery & Psychiatry
.

All patients were evaluated
for neurospecific autoantibodies at the Mayo Neuroimmunological Laboratory.
Includes the following cases: (1) all KLHL11 IgG seropositive cases identified in Mayo Clinic history as of January 2022, (2) high-risk paraneoplastic autoantibody cases meeting the diagnostic criteria for 2021 probable or definitive PNS between January 2001 and February 2022, and (3) other confirmed or probable PNS
between January 2020 and March 2022.
Cases
lacking follow-up data, complete paraneoplastic autoantibody screening, or complete cancer screening were excluded.
Calculate the MATCH score
for each patient.
Calculate sensitivity, specificity, positive predictive value, and negative predictive value
.
We also assessed score performance
based on the area under the subject's operating curve (AUC).

A total of 186 patients with PNS were identified, including 36 KLHL11 IgG seropositive and 138 other specific autoantibody seropositives, including: CRMP5 (n=38), PCA1 (n=36), amphoteric hormones (n=14), ANNA1 (anti-Hu, n=7), ANNA 2 (anti-Ri, n=15), Ma2 (n=11), PCA-Tr (n=4), neurofilaments (n=5), PCA2 (n=1), CASPR2 (n=3), P/Q type voltage-gated calcium channel (n=10), ANNA1 and CRMP5 in combination (n=3), ANNA1 in combination with amphotericin (n=1), and 12 seronegative patients
with probable PNS.
The score detected 31/36 KLHL11 IgG-positive patients with a sensitivity of 86%, which was higher than the sensitivity reported in the paper (78%)
.
Of the 150 patients who were seronegative for KLHL11 IgG, 17 had false-positive scores with a specificity of 89%, lower than previously reported specificity (99%)
.
Patients with MA2 (6/11) and CRMP5 (5/38) had the highest
false-positive rates.
The positive predictive value and negative predictive value when the score was set were 65% and 96% ≥
4 cases, respectively.
Scores showed good discriminating ability, with AUC of 0.
924 (95% CI 0.
885 to 0.
962).

KLHL11 IgG seropositive cases with low MATCH scores and patients with high MATCH scores with replacement autoantibodies

The MATCH score is a comprehensive scoring system based on clinical features and cancer relevance to identify patients
who should be tested for KLHL11 IgG.
While the MATCH score has good sensitivity and specificity for identifying patients who may be KLHL11 IgG seropositive, some cases where germ cell tumors are not detected during the initial evaluation, or those that present with motor neuropathy or borderline encephalitis at the time of initial evaluation may be missed
.
In addition, this score does not explain vestibular lesions (central or peripheral), and even in the absence of hearing loss or tinnitus, vestibular lesions may be a manifestation of
KLHL11 autoimmunity.
This score does not definitively exclude sensorineural hearing loss or cerebellar symptoms due to other causes, including presbycusis deafness or stroke, and should be used
in conjunction with careful neurological evaluation and reasonable exclusion of other causes.
Examining the progression of KLHL11 autoimmune hearing loss may help distinguish it from the slow progression of presbycusis
.
In addition, the score does not dictate whether the scoring variable (symptom or tumor diagnosis) should appear for a limited period of time or whether it can be encountered
at any point in the patient's life.
However, it is important to note that some patients in the KLHL11 IgG seropositive cohort developed symptoms
years after the initial germ cell tumor diagnosis.

In conclusion, the application of MATCH scores in patients suspected of having paraneoplastic syndromes can lead to selection of appropriate patients for KLHL11 IgG testing
.
However, atypical KLHL11 manifestations and/or lack of tumor diagnosis prior to autoantibody evaluation may result in low MATCH scores
.