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Atlas of Antinuclear Antibodies

Structure and function of eukaryotic cell
and outlines of cell cycle

One of the major advantages of detecting and screening autoantibodies by IIF is to find out the localization of recognized cellular antigens in various cell cycles by their staining patterns. It becomes very important to realize the structure of the cell related to the function and localization of the antigens in the cell.

Structure and function of cell

General structure of the eukaryotic cell as HEp-2 cell is shown in Fig. 1. Inside the cell, various organelles including the nucleus, endoplasmic reticulum, golgi apparatus, mitochondria, peroxisomes and lysosomes are recognized. The cell surface is covered by plasma membrane, and the space between the plasma membrane and organelles are occupied by insoluble cytoskelton and soluble cytoplasm.


Nucleus

The nucleus is covered by bi-layer nuclear membrane. The outer nuclear membrane is connected with endoplasmic reticulum and transport of various substances between the nucleus and cytoplasm occurs through nuclear pore complexes. The inner nuclear membrane is connected with lamina. In interphase cells, chromosomes are dispersed into chromatins throughout the nucleoplasm. The chromatins are composed of DNA, histones, and other non-histone proteins. In the granular components of nucleus, precursor mRNA (heterogeneous nuclear RNA; hnRNA) and small RNA-protein complexes (small nuclear ribonucleoproteins; snRNP) for splicing of hnRNA can be found.
In the nucleolus, ribosomal RNA precursors are transcribed and after their processing and assembly, ribosomes are transported to the cytoplasm.


Cytoplasm

Endoplasmic reticulum (ER)
ER are divided into rough surface RER which binds ribosomes on its surface and smooth surface SER. RER is the main site of protein synthesis in the cell and the SER is found abundantly in cells like Leydig cells in the testis which synthesize and secrete steroid hormones. Oxidoreductase systems of NADH and NADPH in the SER membrane are concerned with unsaturation and ω-oxidation of fatty acids and detoxication of xenobiotic substances.

Golgi apparatus
Golgi apparatus is composed of stacks of cisterna and divided into cis, medial and trans regions. It is mainly concerned with the modification (addition of sugar chains) and sorting of the synthesized proteins in RER for secretion and transport in cells.

Mitochondria
Mitochondria are oval in structure. Respiratory chain and ATP synthetase complex for ATP production are in its inner membrane. Enzymes for TCA cycle, fatty acid oxidation and amino acid metabolism, and own protein synthesis system with mitochondrial DNA are in its matrix.

Lysosome
Lysosome is an organelle with monolayer membrane, and it is mainly concerned with the hydrolysis of waste products and toxic substances (proteins, mucopolysaccharides, glycolipids and nucleic acids) by their respective enzymes localized in the matrix where low pH is maintained by the action of H+-ATPase.



Table 1 Antigens recognized by autoantibodies in connective tissue diseases

antinuclear
antibodies
localization recognized
antigens
relevant
diseases
anti-ss-DNA antibody
anti-ds-DNA antibody
anti-polyADP ribose antibody
anti-Scl-70 antibody
anti-centromere antibody
anti-histone antibody
chromatins single stranded DNA (ssDNA)
double-stranded DNA (dsDNA)
poly ADPribose
DNA topoisomerase I
centromere
histone
SLE etc.
SLE
SLE
SSc
CREST
Drug induced lupus
anti-U1RNP antibody
anti-Sm antibody
anti-U2RNP antibody
anti-SS-A/Ro antibody
anti-SS-B/La antibody
anti-PCNA antibody
anti-Ku antibody
nucleus U1RNP
U1, U2, U4/U6, U5 RNP
U2RNP
hY1〜hY5 RNP
RNA polymerase III transcription termination factor
DNA polymerase δ auxiliary factor
DNA-dependent protein kinase activation factor
MCTD
SLE
Overlap syndrome
SS etc.
SS
SLE
Overlap syndrome
anti-U3RNP antibody
anti-7-2(Th)RNP antibody
anti-RNA polymerase I antibody
anti-PM-Scl antibody
anti-NOR-90 antibody
nucleolus U3RNP (Fibrillarin)
RNaseP, RNaseMRP
RNA polymerase I
11 proteins complex (20-110kD)
nucleolus NOR (hUBF)*
SSc
SSc
SSc
Overlap syndrome
SSc

anticytoplasmic
antibodies
localization recognized
antigens
relevant
diseases
anti-Jo-1 antibody
anti-ribosomal antibody
anti-mitochondrial antibody
anti-SS-A/Ro antibody
others (anti actin antibody etc.)
cytoplasm histidyl-tRNA synthetase
60S ribosomal subunit
mitochondria
hY1〜hY5 RNP
PM/DM
SLE
PBC
SS etc.

*human Upstream Binding Factor

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SLE: systemic lupus erythematosus, SSc: systemic sclerosis, MCTD: mixed connective tissue disease, SS: Sjögren's syndrome, PM/DM: polymyositis/dermatomyositis, RA: rheumatoid arthritis, PBC: primary biliary cirrhosis, AIH: autoimmune hepatitis


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