## 2 Mechanisms of Cognitive Dysfunction
### Anti-N-methyl-d-aspartate Receptor Subunit NR2A/B Antibodies
A 21 amino acid sequence (NGMIGEVVYQRAVMAXVGSLTI) was identified using a phage peptide display library to screen antibodies from patients suffering from acute ischemic stroke [54]. This amino acid sequence corresponds to residues 494-514 of the NR2A subunit and bears minor differences to the NR2B subunit [54]. These data suggest that mechanisms for production of anti-NR2A/B antibodies may be operational even in non-autoimmune healthy controls, albeit with different fine antibody specificities. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**References** & **Study Type** & **Number of Subjects** & \begin{tabular}{c} **Amino Acid Sequence** \\ **Used for Immunowassays** \\ \end{tabular} & \
\begin{tabular}{c} **Reported Anti-NR2A/B Values** \\ \end{tabular} &
\begin{tabular}{c} **Essential Findings** \\ \end{tabular} \\ \hline
[9] & Cross-sectional & 412 SLE patients & DWEYSWLSN & Serum optical densities; 19\% of SLE patients & No association between anti-NR2A/B \\  & & & & were anti-NR2/B antibodies positive & antibody status and cognitive impairment \\ \hline
[19] & Cross-sectional & 60 SLE patients & DWEYS & Serum optical densities; 33.3\% of SLE & No association between anti-NR2A/B \\  & & & & patients were anti-NR2/B antibodies positive & antibody status and cognitive impairment \\ \hline
[31] & \
\begin{tabular}{c} Longitudinal \\ (18 months) \\ \end{tabular} &
\begin{tabular}{c} 40 pediatric \\ SLE patients \\ \end{tabular} & DWEYSWLSN & Serum concentration (U/mL) & Association between decline in working memory and an increase in anti-NR2A/B antibodies from baseline \\ \hline
[43] & Cross-sectional & 57 SLE patients & DWEYSWLSN & Serum optical densities; 19\% of SLE patients & 7 of the 31 chronological tests associated \\  & & & & were anti-NR2/B antibodies positive & with positive anti-NR2A/B antibodies \\ \hline
[44] & \
\begin{tabular}{c} Longitudinal \\ (5 years) \\ \end{tabular} &
\begin{tabular}{c} 65 women \\ with SLE \\ \end{tabular} & DWEYS & Serum optical densities; 35\% of SLE patients & No association between anti-NR2A/B \\  & & & & were anti-NR2/B antibodies positive & rise in or persistently elevated anti-NR2A/B \\  & & & & antibodies and cognitive function over 5 years \\ \hline
[45] & Cross-sectional & 93 SLE patients & DWEYSWLSN & Serum optical densities; 25.8\% of SLE patients & No association between anti-NR2A/B \\  & & & & were anti-NR2/B antibodies positive & antibody status and cognitive impairment \\ \hline
[46] & Cross-sectional & \begin{tabular}{c} 43 SLE patients and \\ 27 healthy controls \\ \end{tabular} & DWEYSWLSN & \
\begin{tabular}{c} Serum optical densities; 14\% of SLE patients and \\ 7.4\% of healthy controls were anti-NR2/B \\ antibodies positive \\ \end{tabular} &
\begin{tabular}{c} No association between anti-NR2A/B \\ antibody status and cognitive impairment \\ \end{tabular} \\ \hline
[47] & Cross-sectional & 133 women with SLE & DWEYSWLSN & Not available & Association with impaired performance in attention and executive function with positive anti-NR2A/B antibodies \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Human studies on the association between anti-NR2A/B antibodies and cognitive dysfunction in systemic lupus erythematosus (SLE) patients.